Salts and crystal forms of gaba-a positive allosteric modulator

ABSTRACT

The invention relates to salts of Compound 1, crystalline forms thereof, methods of their preparation, pharmaceutical compositions thereof and methods of their use

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/698,057, filed Nov. 27, 2019, which is a continuation of U.S.application Ser. No. 16/517,369, filed Jul. 19, 2019 (now U.S. Pat. No.10,562,930), which claims priority to U.S. Provisional Application No.62/725,805, filed Aug. 31, 2018, all of which are hereby incorporated byreference in their entirety herein.

FIELD OF THE DISCLOSURE

The present disclosure relates to salts of3α-hydroxy-3β-methoxymethyl-21-(1′-imidazolyl)-5α-pregnan-20-one,crystal forms thereof and processes for preparing such salts and crystalforms.

BACKGROUND OF THE DISCLOSURE

3α-Hydroxy-3β-methoxymethyl-21-(1′-imidazolyl)-5α-pregnan-20-one(Compound 1) is a synthetic neuroactive steroid. Its primary moleculartarget is the γ-aminobutyric acid type A (GABA_(A)) receptor, where itacts as a positive allosteric modulator (PAM) of channel function. Thestructural formula of Compound 1 appears below.

Neuroactive steroid GABA_(A) PAMs have demonstrated clinical efficacy inepilepsy, post-partum depression, and major depression.

There is a need for isolable, stable and water-soluble Compound 1 saltsand processes for making the same.

SUMMARY OF THE DISCLOSURE

This disclosure provides salts of Compound 1 and methods of making suchsalts. In some embodiments, the salts of Compound 1 are crystalline. Thedisclosure also provides pharmaceutical compositions comprising salts ofCompound 1.

In some embodiments, the present disclosure provides hydrobromide,citrate, malate, maleate, mesylate, phosphate, tartrate, hydrochloride,tosylate, glucuronate, ethanesulfonate, fumarate, sulfate,napthalene-2-sulfonate, ascorbate, oxalate, napthalene-1,5-disulfonate,malonate, aminosalicylate, benzenesulfonate, isethionate, gentisate,1-hydroxy-2-napthoate, dichloroacetate, cyclamate, andethane-1,2-disulfonate salts of Compound 1.

In some embodiments, the present disclosure provides crystalline formsof hydrobromide, citrate, malate, maleate, mesylate, phosphate,tartrate, hydrochloride, tosylate, glucuronate, ethanesulfonate,fumarate, sulfate, napthalene-2-sulfonate, ascorbate, oxalate,napthalene-1,5-disulfonate, malonate, aminosalicylate, benzenesulfonate,isethionate, gentisate, 1-hydroxy-2-napthoate, dichloroacetate,cyclamate, and ethane-1,2-disulfonate salts of Compound 1.

In some embodiments, the present disclosure provides hydrobromide saltsof Compound 1. In some embodiments, the present disclosure providescrystalline forms of hydrobromide salts of Compound 1 (“Compound 1HBr”). In one embodiment, the present disclosure provides Compound 1 HBr(Form A). In one embodiment, the present disclosure provides Compound 1HBr (Form B). In one embodiment, the present disclosure providesCompound 1 HBr (Form C). In one embodiment, the present disclosureprovides Compound 1 HBr (Form D). In one embodiment, the presentdisclosure provides Compound 1 HBr (Form E).

In some embodiments, the present disclosure provides citrate salts ofCompound 1. In some embodiments, the present disclosure providescrystalline forms of citrate salts of Compound 1 (“Compound 1 Citrate”).In one embodiment, the present disclosure provides Compound 1 Citrate(Form A). In one embodiment, the present disclosure provides Compound 1Citrate (Form B). In one embodiment, the present disclosure providesCompound 1 Citrate (Form C).

The present disclosure provides methods of administering salts ofCompound 1. In some embodiments, the salts of Compound 1 are orallyadministered. The present disclosure also provides methods of treating adisease, disorder, or condition comprising administering atherapeutically effective amount of a salt of Compound 1. In certainembodiments, the disease, disorder, or condition is selected fromepilepsy, post-partum depression, major depressive disorder, bipolardisorder, treatment resistant depression and anxiety.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an x-ray powder diffraction (XRPD) pattern of Compound 1free base (Pattern A).

FIG. 2 shows an XRPD pattern of Compound 1 HBr (Form A).

FIG. 3 shows a differential scanning calorimetry (DSC) thermogram and athermogravimetric analysis (TGA) thermogram of Compound 1 HBr (Form A).

FIG. 4 shows a dynamic vapor sorption (DVS) isotherm plot for Compound 1HBr (Form A).

FIG. 5 shows an XRPD pattern of Compound 1 HBr (Form B).

FIG. 6 shows a differential scanning calorimetry (DSC) thermogram and athermogravimetric analysis (TGA) thermogram of Compound 1 HBr (Form B).

FIG. 7 shows a dynamic vapor sorption (DVS) isotherm plot for Compound 1HBr (Form B).

FIG. 8 shows an XRPD pattern of Compound 1 HBr (Form C).

FIG. 9 shows a differential scanning calorimetry (DSC) thermogram and athermogravimetric analysis (TGA) thermogram of Compound 1 HBr (Form C).

FIG. 10 shows a dynamic vapor sorption (DVS) isotherm plot for Compound1 HBr (Form C).

FIG. 11 shows an XRPD pattern of Compound 1 HBr (Form D).

FIG. 12 shows a differential scanning calorimetry (DSC) thermogram and athermogravimetric analysis (TGA) thermogram of Compound 1 HBr (Form D).

FIG. 13 shows an XRPD pattern of Compound 1 HBr (Form E).

FIG. 14 shows a differential scanning calorimetry (DSC) thermogram and athermogravimetric analysis (TGA) thermogram of Compound 1 HBr (Form E).

FIG. 15 shows an XRPD pattern of Compound 1 Citrate (Form A).

FIG. 16 shows a DSC thermogram and a TGA thermogram of Compound 1Citrate (Form A).

FIG. 17 shows a DVS isotherm plot for Compound 1 Citrate (Form A).

FIG. 18 shows an XRPD pattern of Compound 1 Citrate (Form B).

FIG. 19 shows a DSC thermogram and a TGA thermogram of Compound 1Citrate (Form B).

FIG. 20 shows a DVS isotherm plot for Compound 1 Citrate (Form B).

FIG. 21 shows an XRPD pattern of Compound 1 Citrate (Form C).

FIG. 22 shows an XRPD pattern of Compound 1 Mesylate (Form A).

FIG. 23 shows a DSC thermogram and a TGA thermogram of Compound 1Mesylate (Form A).

FIG. 24 shows a DVS isotherm plot for Compound 1 Mesylate (Form A).

FIG. 25A shows an XRPD pattern of Compound 1 Mesylate (Form B).

FIG. 25B shows an XRPD pattern of Compound 1 Mesylate (Form C).

FIG. 26 shows an XRPD pattern of Compound 1 Mesylate (Form D).

FIG. 27 shows an XRPD pattern of Compound 1 Phosphate (Form A).

FIG. 28 shows a DSC thermogram and a TGA thermogram of Compound 1Phosphate (Form A).

FIG. 29 shows a DVS isotherm plot for Compound 1 Phosphate (Form A).

FIG. 30 shows an XRPD pattern of Compound 1 L(+)-Tartrate (Form A).

FIG. 31 shows a DSC thermogram and a TGA thermogram of Compound 1L(+)-Tartrate (Form A).

FIG. 32 shows a DVS isotherm plot for Compound 1 L(+)-Tartrate (Form A).

FIG. 33 shows an XRPD pattern of Compound 1 L(+)-Tartrate (Form B).

FIG. 34 shows a DSC thermogram and a TGA thermogram of Compound 1L(+)-Tartrate (Form B).

FIG. 35 shows a DVS isotherm plot for Compound 1 L(+)-Tartrate (Form B).

FIG. 36 shows an XRPD pattern of Compound 1 Fumarate (Form A).

FIG. 37 shows a DSC thermogram and a TGA thermogram of Compound 1Fumarate (Form A).

FIG. 38 shows an XRPD pattern of Compound 1 Fumarate (Form B).

FIG. 39 shows a DSC thermogram and a TGA thermogram of Compound 1Fumarate (Form B).

FIG. 40 shows a DVS isotherm plot for Compound 1 Fumarate (Form B).

FIG. 41 shows an XRPD pattern of Compound 1 Fumarate (Form C).

FIG. 42 shows an XRPD pattern of Compound 1 Fumarate (Form D).

FIG. 43 shows an XRPD pattern of Compound 1 Tosylate (Form A).

FIG. 44 shows a DSC thermogram and a TGA thermogram of Compound 1Tosylate (Form A).

FIG. 45 shows a DVS isotherm plot for Compound 1 Tosylate (Form A).

FIG. 46 shows an XRPD pattern of Compound 1 Tosylate (Form B).

FIG. 47 shows an XRPD pattern of Compound 1 Tosylate (Form C).

FIG. 48 shows an XRPD pattern of Compound 1 Glucuronate (Form A).

FIG. 49 shows a DSC thermogram and a TGA thermogram of Compound 1Glucuronate (Form A).

FIG. 50 shows a DVS isotherm plot for Compound 1 Glucuronate (Form A).

FIG. 51 shows an XRPD pattern of Compound 1 Glucuronate (Form B).

FIG. 52 shows an XRPD pattern of Compound 1 Ethanesulfonate (Form A).

FIG. 53 shows a DSC thermogram and a TGA thermogram of Compound 1Ethanesulfonate (Form A).

FIG. 54 shows a DVS isotherm plot for Compound 1 Ethanesulfonate (FormA).

FIG. 55 shows an XRPD pattern of Compound 1 Sulfate (Form A).

FIG. 56 shows a DSC thermogram and a TGA thermogram of Compound 1Sulfate (Form A).

FIG. 57 shows a DVS isotherm plot for Compound 1 Sulfate (Form A).

FIG. 58 shows an XRPD pattern of Compound 1 Ascorbate (Form A).

FIG. 59 shows a DSC thermogram and a TGA thermogram of Compound 1Ascorbate (Form A).

FIG. 60 shows a DVS isotherm plot for Compound 1 Ascorbate (Form A).

FIG. 61 shows an XRPD pattern of Compound 1 Ascorbate (Form B).

FIG. 62 shows an XRPD pattern of Compound 1 Napadisylate (Form A).

FIG. 63 shows a DSC thermogram and a TGA thermogram of Compound 1Napadisylate (Form A).

FIG. 64 shows a DVS isotherm plot for Compound 1 Napadisylate (Form A).

FIG. 65 shows an XRPD pattern of Compound 1 Napadisylate (Form B).

FIG. 66 shows an XRPD pattern of Compound 1 Malonate (Form A).

FIG. 67 shows a DSC thermogram and a TGA thermogram of Compound 1Malonate (Form A).

FIG. 68 shows an XRPD pattern of Compound 1 Besylate (Form A).

FIG. 69 shows a DSC thermogram and a TGA thermogram of Compound 1Besylate (Form A).

FIG. 70 shows a DVS isotherm plot for Compound 1 Besylate (Form A).

FIG. 71 shows an XRPD pattern of Compound 1 Besylate (Form B).

FIG. 72 shows an XRPD pattern of Compound 1 Isethionate (Form A).

FIG. 73 shows a DSC thermogram and a TGA thermogram of Compound 1Isethionate (Form A).

FIG. 74 shows a DVS isotherm plot for Compound 1 Isethionate (Form A).

FIG. 75 shows an XRPD pattern of Compound 1 Isethionate (Form B).

FIG. 76 shows an XRPD pattern of Compound 1 Gentisate (Form A).

FIG. 77 shows a DSC thermogram and a TGA thermogram of Compound 1Gentisate (Form A).

FIG. 78 shows a DVS isotherm plot for Compound 1 Gentisate (Form A).

FIG. 79 shows an XRPD pattern of Compound 1 Gentisate (Form B).

FIG. 80 shows an XRPD pattern of Compound 1 Gentisate (Form C).

FIG. 81 shows an XRPD pattern of Compound 1 1-Hydroxy-2-napthoate (FormA).

FIG. 82 shows a DSC thermogram and a TGA thermogram of Compound 11-Hydroxy-2-napthoate (Form A).

FIG. 83 shows a DVS isotherm plot for Compound 1 1-Hydroxy-2-napthoate(Form A).

FIG. 84 shows an XRPD pattern of Compound 1 1-Hydroxy-2-napthoate (FormB).

FIG. 85 shows an XRPD pattern of Compound 1 1-Hydroxy-2-napthoate (FormC).

FIG. 86 shows an XRPD pattern of Compound 1 1-Hydroxy-2-napthoate (FormD).

FIG. 87 shows an XRPD pattern of Compound 1 Cyclamate (Form A).

FIG. 88 shows a DSC thermogram and a TGA thermogram of Compound 1Cyclamate (Form A).

FIG. 89 shows a DVS isotherm plot for Compound 1 Cyclamate (Form A).

FIG. 90 shows an XRPD pattern of Compound 1 Ethane-1, 2-disulfonate(Form A).

FIG. 91 shows a DSC thermogram and a TGA thermogram of Compound 1Ethane-1, 2-disulfonate (Form A).

FIG. 92 shows a DVS isotherm plot for Compound 1 Ethane-1, 2-disulfonate(Form A).

FIG. 93 shows an XRPD pattern of Compound 1 Ethane-1, 2-disulfonate(Form B).

FIG. 94 shows an XRPD pattern of Compound 1 Dichloroacetate (Form A).

FIG. 95 shows a DSC thermogram and a TGA thermogram of Compound 1Dichloroacetate (Form A).

FIG. 96 shows a DVS isotherm plot for Compound 1 Dichloroacetate (FormA).

FIG. 97 shows an XRPD pattern of Compound 1 L-Malate (Form A).

FIG. 98 shows a DSC thermogram and a TGA thermogram of Compound 1L-Malate (Form A).

FIG. 99 shows a DVS isotherm plot for Compound 1 L-Malate (Form A).

FIG. 100 shows an XRPD pattern of Compound 1 L-Malate (Form B).

FIG. 101 shows a DSC thermogram and a TGA thermogram of Compound 1L-Malate (Form B).

FIG. 102 shows a DVS isotherm plot for Compound 1 L-Malate (Form B).

FIG. 103 shows an XRPD pattern of Compound 1 Hydrochloride (Form A).

FIG. 104 shows a DSC thermogram and a TGA thermogram of Compound 1Hydrochloride (Form A).

FIG. 105 shows a DVS isotherm plot for Compound 1 Hydrochloride (FormA).

FIG. 106 shows an XRPD pattern of Compound 1 Hydrochloride (Form B).

FIG. 107 shows a DSC thermogram and a TGA thermogram of Compound 1Hydrochloride (Form B).

FIG. 108 shows a DVS isotherm plot for Compound 1 Hydrochloride (FormB).

FIG. 109 shows an XRPD pattern of Compound 1 Hydrochloride (Form C).

FIG. 110 shows a DSC thermogram and a TGA thermogram of Compound 1Hydrochloride (Form C).

FIG. 111 shows a DVS isotherm plot for Compound 1 Hydrochloride (FormC).

FIG. 112 shows an XRPD pattern of Compound 1 Napsylate (Form A).

FIG. 113 shows a DSC thermogram and a TGA thermogram of Compound 1Napsylate (Form A).

FIG. 114 shows a DVS isotherm plot for Compound 1 Napsylate (Form A).

FIG. 115 shows an XRPD pattern of Compound 1 Napsylate (Form B).

FIG. 116 shows an XRPD pattern of Compound 1 Oxalate (Form A).

FIG. 117 shows a DSC thermogram and a TGA thermogram of Compound 1Oxalate (Form A).

FIG. 118 shows a DVS isotherm plot for Compound 1 Oxalate (Form A).

FIG. 119 shows an XRPD pattern of Compound 1 Oxalate (Form B).

FIG. 120 shows an XRPD pattern of Compound 1 P-Aminosalicylate (Form A).

FIG. 121 shows a DSC thermogram and a TGA thermogram of Compound 1P-Aminosalicylate (Form A).

FIG. 122 shows a DVS isotherm plot for Compound 1 P-Aminosalicylate(Form A).

FIG. 123 shows an XRPD pattern of Compound 1 P-Aminosalicylate (Form B).

FIG. 124 shows an XRPD pattern of Compound 1 Maleate (Form A).

DETAILED DESCRIPTION OF THE DISCLOSURE Definitions

The term “about” when immediately preceding a numerical value means arange (e.g., plus or minus 10% of that value). For example, “about 50”can mean 45 to 55, “about 25,000” can mean 22,500 to 27,500, etc.,unless the context of the disclosure indicates otherwise, or isinconsistent with such an interpretation. For example in a list ofnumerical values such as “about 49, about 50, about 55, . . . ”, “about50” means a range extending to less than half the interval(s) betweenthe preceding and subsequent values, e.g., more than 49.5 to less than52.5. Furthermore, the phrases “less than about” a value or “greaterthan about” a value should be understood in view of the definition ofthe term “about” provided herein. Similarly, the term “about” whenpreceding a series of numerical values or a range of values (e.g.,“about 10, 20, 30” or “about 10-30”) refers, respectively to all valuesin the series, or the endpoints of the range.

Throughout this disclosure, various patents, patent applications andpublications (including non-patent publications) are referenced. Thedisclosures of these patents, patent applications and publications intheir entireties are incorporated into this disclosure by reference forall purposes in order to more fully describe the state of the art asknown to those skilled therein as of the date of this disclosure. Thisdisclosure will govern in the instance that there is any inconsistencybetween the patents, patent applications and publications cited and thisdisclosure.

For convenience, certain terms employed in the specification, examplesand claims are collected here. Unless defined otherwise, all technicaland scientific terms used in this disclosure have the same meanings ascommonly understood by one of ordinary skill in the art to which thisdisclosure belongs.

The terms “administer,” “administering” or “administration” as usedherein refer to either directly administering Compound 1 orpharmaceutically acceptable salt thereof or a composition comprisingCompound 1 or pharmaceutically acceptable salt to a patient.

The terms “aprotic solvent,” “nonprotic solvent” or “non-protic solvent”as used herein refers to an organic solvent or a mixture of organicsolvents that is not readily deprotonated in the presence of a stronglybasic reactant. Non-limiting examples of non-protic solvents includeethers, dimethylformamide (DMF), dimethylacetamide (DMAC),1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU),1,3-dimethyl-2-imidazolidinone (DMI), N-methylpyrrolidinone (NMP),formamide, N-methylacetamide, N-methylformamide, acetonitrile, dimethylsulfoxide, propionitrile, ethyl formate, methyl acetate, methyl isobutylketone, hexachloroacetone, acetone, ethyl methyl ketone, methyl ethylketone (MEK), ethyl acetate, isopropyl acetate, sulfolane,N,N-dimethylpropionamide, tetramethylurea, nitromethane, nitrobenzene,or hexamethylphosphoramide, diethoxymethane, tetrahydrofuran,1,3-dioxane, 1,4-dioxane, furan, diethyl ether, tetrahydropyran,diisopropyl ether, dibutyl ether, ethylene glycol dimethyl ether,ethylene glycol diethyl ether, diethylene glycol dimethyl ether,diethylene glycol diethyl ether, triethylene glycol dimethyl ether,anisole, t-butyl methyl ether, and the like.

The term “carrier” as used herein encompasses carriers, excipients, anddiluents, meaning a material, composition or vehicle, such as a liquidor solid filler, diluent, excipient, solvent or encapsulating materialinvolved in carrying or transporting a pharmaceutical agent from oneorgan, or portion of the body, to another organ or portion of the body.

The term “disorder” is used in this disclosure to mean, and is usedinterchangeably with, the terms disease, condition, or illness, unlessotherwise indicated.

The terms “effective amount” and “therapeutically effective amount” areused interchangeably in this disclosure and refer to an amount of acompound, or a salt, solvate or ester thereof, that, when administeredto a patient, is capable of performing the intended result. For example,an effective amount of a salt of Compound 1 is that amount that isrequired to reduce at least one symptom of depression in a patient. Theactual amount that comprises the “effective amount” or “therapeuticallyeffective amount” will vary depending on a number of conditionsincluding, but not limited to, the severity of the disorder, the sizeand health of the patient, and the route of administration. A skilledmedical practitioner can readily determine the appropriate amount usingmethods known in the medical arts.

The term “isomer” refers to compounds having the same chemical formulabut may have different stereochemical formula, structural formula, orspecial arrangements of atoms. Examples of isomers includestereoisomers, diastereomers, enantiomers, conformational isomers,rotamers, geometric isomers, and atropisomers.

The term “peak” refers to a line having a substantial intensity in theXRPD diffractogram (or pattern) obtained from a sample using standardXRPD collection techniques. For example, a peak is a line in the XRPDdiffractogram having an intensity that is, for example, at least about10% of the intensity of the largest peak in the XRPD diffractogram.

The phrase “pharmaceutically acceptable” as used herein refers to thosecompounds, materials, compositions, and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit/risk ratio.

The term “protic solvent” as used herein refers to a solvent or asolvent mixture that is capable of functioning as an acid for purposesof protonating any unreacted, strongly basic reaction intermediates.Non-limiting examples of protic solvents include water, methanol,ethanol, 2-nitroethanol, 2-fluoroethanol, 2,2,2-trifluoroethanol,ethylene glycol, 1-propanol, 2-propanol, 2-methoxyethanol, 1-butanol,2-butanol, i-butyl alcohol, t-butyl alcohol, 2-ethoxyethanol, diethyleneglycol, 1-, 2-, or 3-pentanol, neo-pentyl alcohol, t-pentyl alcohol,diethylene glycol monomethyl ether, diethylene glycol monoethyl ether,cyclohexanol, benzyl alcohol, phenol, glycerol, and the like.

The term “salts” as used herein embraces pharmaceutically acceptablesalts commonly used to form addition salts of free bases. The nature ofthe salt is not critical provided that it is pharmaceuticallyacceptable. The term “salts” also includes solvates of addition salts,such as hydrates, as well as polymorphs of addition salts. Suitablepharmaceutically acceptable acid addition salts can be prepared from aninorganic acid or from an organic acid. In a salt, proton transferoccurs between Compound 1 free base and an organic acid or an inorganicacid. However, in some cases proton transfer is incomplete. In suchcases, Compound 1 and the “co-former” molecules in the solid (i.e.,“co-crystal”) interact through non-ionic forces such as hydrogenbonding.

Where an acid co-former is a solid at about 23° C. (i.e., roomtemperature) and there is no, or partial, proton transfer betweenCompound 1 and the acid co-former, a co-crystal of the co-former andCompound 1 is provided. As used herein, the term “salt” encompassesco-crystal forms of Compound 1.

The term “substantially similar” as used herein means an analyticalspectrum, such as XRPD pattern, DSC thermogram, etc., which resemblesthe reference spectrum to a great degree in both the peak locations andtheir intensity.

The term “treating” as used herein with regard to a patient, refers toimproving at least one symptom of the patient's disorder. Treating canbe curing, improving, or at least partially ameliorating a disorder.

The term “therapeutic effect” as used herein refers to a desired orbeneficial effect provided by the method and/or the composition. Forexample, the method for treating depression provides a therapeuticeffect when the method reduces at least one symptom of depression in apatient.

As used herein, the symbol “≤” means “not more than” or “equal to orless than”; “<” means “less than”; “≥” means “not less than” or “equalto or more than”; and “>” means “more than”. Furthermore, the numericalnumbers, when used herein in connection with purity or impurity content,include not only the exact number but also the approximate range aroundthe number. For example, the phrase “purity of 99.0%” denotes a purityof about 99.0%.

Salts of Compound 1

Compound 1 is a neuroactive steroid GABA-A positive allosteric modulator(PAM) with high potency similar to clinical stage neuroactive steroids(allopregnanolone, ganaxolone, SAGE-217, alphaxolone). Compound 1 ispoorly soluble at the pH found in the lower GI tract, which may limitCompound 1's oral bioavailability.

The synthesis of Compound 1 is described in U.S. Publication Nos.2004/034002 and 2009/0118248; crystalline polymorph of Compound 1 freebase is described in U.S. Publication No. 2006/0074059 andpharmaceutical compositions containing Compound 1 are described in U.S.Publication No. 2009/0131383, which are hereby incorporated by referencein their entirety for all purposes.

The present disclosure provides salts of Compound 1 and crystallineforms thereof.

Crystalline Salts of Compound 1

In some embodiments, the present disclosure provides crystalline formsof a salt of Compound 1. Polymorphism can be characterized as theability of a compound to crystallize into different crystal forms whilemaintaining the same structural formula (i.e., the covalent bonds in thecompound are the same in different crystal forms). A crystallinepolymorph of a given drug substance is chemically identical to any othercrystalline polymorph of that drug substance in containing the sameatoms bonded to one another in the same way, but differs in its crystalforms, which can affect one or more physical properties, such asstability, solubility, melting point, bulk density, flow properties,etc., or pharmacological properties such as bioavailability, etc.

In some embodiments, the crystalline forms are characterized by theinterlattice plane intervals determined by an X-ray powder diffractionpattern (XRPD). The XRPD diffractogram is typically represented by adiagram plotting the intensity of the peaks versus the location of thepeaks, i.e., diffraction angle 2θ (two-theta) in degrees. Thecharacteristic peaks of a given XRPD diffractogram can be selectedaccording to the peak locations and their relative intensity toconveniently distinguish this crystalline structure from others. The %intensity of the peaks relative to the most intense peak may berepresented as I/Io.

Those skilled in the art recognize that the measurements of the XRPDpeak locations and/or intensity for a given crystalline form of the samecompound will vary within a margin of error. The values of degree 2θallow appropriate error margins. Typically, the error margins arerepresented by “±”. For example, the degree 20 of about “8.716±0.3”denotes a range from about 8.716+0.3, i.e., about 9.016, to about8.716−0.3, i.e., about 8.416. Depending on the sample preparationtechnique, the calibration technique applied to the instrument, humanoperational variation, and etc., those skilled in the art recognize thatthe appropriate error of margins for an XRPD can be about ±0.7; ±0.6;±0.5; ±0.4; ±0.3; ±0.2; ±0.1; ±0.05; or less.

Additional details of the methods and equipment used for the XRPDanalysis are described in the Examples section.

In some embodiments, the crystalline forms are characterized byDifferential Scanning calorimetry (DSC). The DSC thermogram is typicallyexpressed by a diagram plotting the normalized heat flow in units ofWatts/gram (“W/g”) versus the measured sample temperature in degree C.The DSC thermogram is usually evaluated for extrapolated onset and end(outset) temperatures, peak temperature, and heat of fusion. A peakcharacteristic value of a DSC thermogram is often used as thecharacteristic peak to distinguish this crystalline structure fromothers.

Those skilled in the art recognize that the measurements of the DSCthermogram for a given crystalline form of the same compound will varywithin a margin of error. The values of a single peak characteristicvalue, expressed in degree C., allow appropriate error margins.Typically, the error margins are represented by “±”. For example, thesingle peak characteristic value of about “53.09±2.0” denotes a rangefrom about 53.09+2, i.e., about 55.09, to about 53.09−2, i.e., about51.09. Depending on the sample preparation techniques, the calibrationtechniques applied to the instruments, human operational variations, andetc., those skilled in the art recognize that the appropriate error ofmargins for a single peak characteristic value can be ±2.5; ±2.0; ±1.5;±1.0; ±0.5; or less.

Additional details of the methods and equipment used for the DSCthermogram analysis are described in the Examples section.

Hydrobromide Salt

In some embodiments, the present disclosure provides a hydrobromide saltof Compound 1 (“Compound 1 HBr”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 HBr.

In one embodiment, the present disclosure provides Compound 1 HBr (FormA). In some embodiments, the Compound 1 HBr (Form A) exhibits an XRPDcomprising one or more peaks at about 7.6, 15.2, 16.3, 19.8 and 22.9degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In anotherembodiment, the XRPD of the Compound 1 HBr (Form A) further comprisesone or more peaks at about 15.5, 19.2, 20.6, 26.1, and 31.3 degreestwo-theta with the margin of error of about ±0.5; about ±0.4; about±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 HBr (Form A) exhibits an XRPD comprisingpeaks shown in Table 1 below:

TABLE 1 XRPD Table of Compound 1 HBr (Form A) 2-Theta Intensity % 7.6100 9.6 11.4 11.6 3.1 11.9 2.8 13.2 2.8 13.9 5.6 15.2 47.9 15.5 24.416.3 82.8 18.5 2.0 19.2 11.6 19.8 28.8 20.6 15.0 21.2 2.9 22.3 3.3 22.953.3 23.2 3.4 23.7 11.1 24.6 3.7 25.4 1.6 26.1 20.7 26.4 4.8 27.0 4.427.4 2.5 28.0 2.0 28.9 6.0 30.3 3.1 30.7 4.7 31.3 15.6 31.7 2.1 32.5 1.533.0 4.4 33.6 1.5 34.0 2.1 34.7 3.9 35.6 2.2 39.1 4.8

Some embodiments provide Compound 1 HBr (Form A), wherein in the rangefrom 15.2±0.2 to 16.3±0.2 degrees two-theta in the XRPD pattern, theForm A exhibits only three peaks.

In some embodiments, the Compound 1 HBr (Form A) exhibits an XRPD thatis substantially similar to FIG. 2.

In some embodiments, the Compound 1 HBr (Form A) exhibits a DSCthermogram comprising a sharp endotherm at about 243.1° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 HBr (Form A) exhibitsa DSC thermogram that is substantially similar to FIG. 3.

In some embodiments, the Compound 1 HBr (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 3. In otherembodiments, the TGA thermogram of the Compound 1 HBr (Form A) exhibitsa weight loss of about 0.0 to 1.9% in the temperature range of 25 to230° C.

In some embodiments, the Compound 1 HBr (Form A) exhibits a DVS isothermplot that is substantially similar to FIG. 4. In other embodiments, theCompound 1 HBr (Form A) exhibits a gravimetric moisture sorption ofabout 1.1% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 HBr (FormB). In some embodiments, the Compound 1 HBr (Form B) exhibits an XRPDcomprising one or more peaks at about 3.6, 16.3, 17.7, 21.4 and 23.5degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In anotherembodiment, the XRPD of the Compound 1 HBr (Form B) further comprisesone or more peaks at about 14.4, 18.7, 24.8, 27.3 and 28.2 degreestwo-theta with the margin of error of about ±0.5; about ±0.4; about±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 HBr (Form B) exhibits an XRPD comprisingpeaks shown in Table 2 below:

TABLE 2 XRPD Table of Compound 1 HBr (Form B) 2-Theta Intensity % 3.6 518.9 18.8 14.1 17.8 14.4 37.5 16.3 52.6 16.7 19.8 17.7 100 18.7 32.2 19.323.6 19.5 20 21.4 76 21.8 17.6 22.8 14.8 23.5 41.8 24.3 14.4 24.8 30.725.7 23.9 25.9 11.4 26.6 14 27.3 29.2 27.7 11.2 28.2 28.6 30.2 5.4 30.37.5 30.9 12.5 33.8 12.7 34.5 11 35.0 13.1 35.9 11.6

In some embodiments, the Compound 1 HBr (Form B) exhibits an XRPD thatis substantially similar to FIG. 5.

In some embodiments, the Compound 1 HBr (Form B) exhibits a DSCthermogram comprising an endotherm at about 121° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 HBr (Form B) exhibits a DSCthermogram that is substantially similar to FIG. 6.

In some embodiments, the Compound 1 HBr (Form B) exhibits a TGAthermogram that is substantially similar to FIG. 6. In otherembodiments, the TGA thermogram of the Compound 1 HBr (Form B) exhibitsa weight loss of about 0.0 to 3.4% in the temperature range of 25 to120° C.

In some embodiments, the Compound 1 HBr (Form B) exhibits a DVS isothermplot that is substantially similar to FIG. 7. In other embodiments, theCompound 1 HBr (Form B) exhibits a gravimetric moisture sorption ofabout 0.2% (by weight) at 80% Relative Humidity.

In some embodiments, the Compound 1 HBr (Form B) is defined by unit cellparameters substantially similar to the following: a=9.3 (4) Å; b=10.8(4) Å; c=25.2 (11) Å; α=90′; β=90°; γ=90′; Space group P2₁2₁2₁;Molecules/asymmetric unit 1, wherein the crystalline form is at about120 K.

In one embodiment, the present disclosure provides Compound 1 HBr (FormC). In some embodiments, the Compound 1 HBr (Form C) exhibits an XRPDcomprising one or more peaks at about 6.9, 13.8, 20.8, 21.6 and 27.7degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In anotherembodiment, the XRPD of the Compound 1 HBr (Form C) further comprisesone or more peaks at about 8.8, 25.6, 27.5, 36.2 and 37.3 degreestwo-theta with the margin of error of about ±0.5; about ±0.4; about±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 HBr (Form C) exhibits an XRPD comprisingpeaks shown in Table 3 below:

TABLE 3 XRPD Table of Compound 1 HBr (Form C) 2-Theta Intensity % 3.48.3 6.9 62.4 8.8 10.2 10.9 7.0 13.8 32.4 16.3 3.2 17.7 8.9 19.3 5.0 20.8100 21.6 20.5 23.6 8.5 23.8 3.2 25.6 14.1 27.5 14.8 27.7 70.1 34.8 8.436.2 10.2 37.3 14.3

In some embodiments, the Compound 1 HBr (Form C) exhibits an XRPD thatis substantially similar to FIG. 8.

In some embodiments, the Compound 1 HBr (Form C) exhibits a DSCthermogram comprising a sharp endotherm at about 141° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 HBr (Form C) exhibits a DSCthermogram that is substantially similar to FIG. 9.

In some embodiments, the Compound 1 HBr (Form C) exhibits a TGAthermogram that is substantially similar to FIG. 9. In otherembodiments, the TGA thermogram of the Compound 1 HBr (Form C) exhibitsa weight loss of about 0.0 to 4.1% in the temperature range of 25 to170° C.

In some embodiments, the Compound 1 HBr (Form C) exhibits a DVS isothermplot that is substantially similar to FIG. 10. In other embodiments, theCompound 1 HBr (Form C) exhibits a gravimetric moisture sorption ofabout 0.25% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 HBr (FormD). In some embodiments, the Compound 1 HBr (Form D) exhibits an XRPDcomprising one or more peaks at about 14.7, 15.2, 15.6, 16.4, and 23.1degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In anotherembodiment, the XRPD of the Compound 1 HBr (Form D) further comprisesone or more peaks at about 18.2, 19.9, 21.3, 22.2, and 23.4 degreestwo-theta with the margin of error of about ±0.5; about ±0.4; about±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 HBr (Form D) exhibits an XRPD comprisingpeaks shown in Table 4 below:

TABLE 4 XRPD Table of Compound 1 HBr (Form D) 2-Theta Intensity % 7.727.7 9.1 2.6 9.7 12.1 11.9 12.0 12.7 14.5 13.3 6.6 14.0 12.4 14.7 51.515.2 100.0 15.6 55.3 16.1 27.9 16.4 52.4 17.9 31.1 18.2 40.0 18.8 34.919.4 36.2 19.9 47.0 20.7 23.5 21.3 41.0 22.2 39.1 23.1 56.6 23.4 48.223.8 30.7 24.2 24.6 24.8 21.8 26.2 31.4 26.6 20.1 27.5 16.4 29.0 11.329.5 18.7 29.7 21.6 30.4 21.1 31.4 14.1 32.7 12.4 33.5 9.7 35.3 10.239.3 10.3

In some embodiments, the Compound 1 HBr (Form D) exhibits an XRPD thatis substantially similar to FIG. 11.

In some embodiments, the Compound 1 HBr (Form D) exhibits a DSCthermogram comprising a sharp endotherm at about 248° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 HBr (Form D) exhibits a DSCthermogram that is substantially similar to FIG. 12.

In some embodiments, the Compound 1 HBr (Form D) exhibits a TGAthermogram that is substantially similar to FIG. 12. In otherembodiments, the TGA thermogram of the Compound 1 HBr (Form D) exhibitsa weight loss of about 0.0 to 1.7% in the temperature range of 29 to150° C.

In some embodiments, the present disclosure provides Compound 1 HBr(Form E). In some embodiments, the Compound 1 HBr (Form E) exhibits anXRPD comprising one or more peaks at about 7.6, 15.2, 16.3, 22.9 and23.2 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 HBr (Form E) furthercomprises one or more peaks at about 9.6, 17.4, 22.4, 23.6 and 31.2degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 HBr (Form E) exhibits an XRPD comprisingpeaks shown in Table 5 below:

TABLE 5 XRPD Table of Compound 1 HBr (Form E) 2-Theta Intensity % 7.6100 9.6 6.1 11.7 1.4 12.3 4.5 12.8 2.3 13.1 1.9 14 2.3 15.2 58.3 16.353.5 17.4 14 19.2 1.6 19.9 4 20.1 5.8 21.2 1.8 22.4 6.8 22.9 47.9 23.219.9 23.6 8.2 23.9 2.1 24.8 1.7 25.4 3.5 25.8 2.6 26.2 5.5 26.5 5.2 26.71.7 27.4 2.7 28.4 3.2 29.9 4.6 30.6 5 31.2 9 33.5 2.1 35.1 3.5 36.5 2.239 3.1 39.5 1.6

Some embodiments provide Compound 1 HBr (Form E), wherein in the rangefrom 15.2±0.2 to 16.3±0.2 degrees two-theta in the XRPD pattern, theForm E exhibits only two peaks.

In some embodiments, the Compound 1 HBr (Form E) exhibits an XRPD thatis substantially similar to FIG. 13.

In some embodiments, the Compound 1 HBr (Form E) exhibits a DSCthermogram comprising a sharp endotherm at about 245° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 HBr (Form E) exhibits a DSCthermogram that is substantially similar to FIG. 14.

In some embodiments, the Compound 1 HBr (Form E) exhibits a TGAthermogram that is substantially similar to FIG. 14. In otherembodiments, the TGA thermogram of the Compound 1 HBr (Form E) exhibitsa weight loss of about 0.0 to 0.5% in the temperature range of 28 to150° C.

In some embodiments, the Compound 1 HBr (Form E) is defined by unit cellparameters substantially similar to the following: a=7.5 (10) Å; b=15.0(2) Å; c=23.0 (2) Å; α=90°; β=90°; γ=90°; Space group P2₁2₁2₁;Molecules/asymmetric unit 1, wherein the crystalline form is at about120 K.

In some embodiments, the Compound 1 HBr (Form E) is defined by unit cellparameters substantially similar to the following: a=23.3 (5) Å; b=15.0(3) Å; c=7.5 (10) Å; α=90°; β=90°; γ=90°; Space group P2₁2₁2₁;Molecules/asymmetric unit 1, wherein the crystalline form is at about298 K.

Citrate Salt

In some embodiments, the present disclosure provides a citrate salt ofCompound 1 (“Compound 1 Citrate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Citrate.

In one embodiment, the present disclosure provides Compound 1 Citrate(Form A). In some embodiments, the Compound 1 Citrate (Form A) exhibitsan XRPD comprising one or more peaks at about 5.7, 11.9, 17.1, 20.1, and20.3 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Citrate (Form A) furthercomprises one or more peaks at about 12.7, 13.0, 13.6, 15.3, and 16.8degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 Citrate (Form A) exhibits an XRPD comprisingpeaks shown in Table 6 below:

TABLE 6 XRPD Table of Compound 1 Citrate (Form A) 2-Theta Intensity (%)5.7 100 8.2 18.5 10.3 4.3 10.6 12 11.4 12.6 11.9 38 12.5 19 12.7 19.613.0 22.4 13.6 21.2 13.9 14.1 14.1 14.2 14.7 5 15.3 21.8 16.8 30.6 17.139.7 17.5 11.4 18.0 14.1 18.7 10.6 19.0 18.3 19.4 14.5 19.7 12.1 20.137.7 20.3 63.7 20.7 11.8 21.3 12.7 21.6 9.9 22.4 11.3 22.8 13.2 23.4 723.9 5.2 24.6 5.7 25.0 4.6 25.8 19.3 26.2 6.3 26.5 6.8 27.2 4.8 28.2 6.528.6 5.8 29.5 6.7 30.5 5.4 31.3 5.8 32.8 4.6 37.1 5.9

In some embodiments, the Compound 1 Citrate (Form A) exhibits an XRPDcomprising peaks at about: 5.7±0.2; 12.5±0.2 and 13.0±0.2; or 5.7±0.2,12.5±0.2 and 20.1±0.2; or 5.7±0.2; 12.5±0.2 and 20.3±0.2; or 5.7±0.2;12.7±0.2 and 13.0±0.2; or 5.7±0.2; 12.7±0.2 and 20.3±0.2; or 5.7±0.2,13.0±0.2 and 20.3±0.2; or 5.7±0.2, 16.8±0.2 and 20.1±0.2; or 5.7±0.2;20.1±0.2 and 20.3±0.2; or 12.5±0.2, 13.0±0.2 and 20.3±0.2; or 12.7±0.2,13.0±0.2 and 20.3±0.2; or 16.8±0.2, 20.1±0.2 and 20.3±0.2 degreestwo-theta.

In some embodiments, the Compound 1 Citrate (Form A) exhibits an XRPDthat is substantially similar to FIG. 15.

In some embodiments, the Compound 1 Citrate (Form A) exhibits a DSCthermogram comprising a endotherm at about 89.0° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In another embodiment, the Compound 1 Citrate (Form A) exhibits aDSC thermogram comprising a sharp endotherm at about 139.5° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 Citrate (Form A)exhibits a DSC thermogram that is substantially similar to FIG. 16.

In some embodiments, the Compound 1 Citrate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 16. In otherembodiments, the TGA thermogram of the Compound 1 Citrate (Form A)exhibits a weight loss of 0.0 to 2.6% in the temperature range of 25 to65° C.

In some embodiments, the Compound 1 Citrate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 17. In otherembodiments, the Compound 1-citrate (Form A) exhibits a gravimetricmoisture sorption of about 3.6% (by weight) at 80% Relative Humidity.

In some embodiments, the Compound 1 Citrate (Form A) is defined by unitcell parameters substantially similar to the following: a=8.9 (10) Å;b=12.2 (10) Å; c=16.5 (10) Å; α=73.7 (10°); β=76.6 (10°); γ=83.2 (10°);Space group P1; Molecules/asymmetric unit 2, wherein the crystallineform is at about 120.00 K.

In one embodiment, the present disclosure provides Compound 1 Citrate(Form B). In some embodiments, the Compound 1 Citrate (Form B) exhibitsan XRPD comprising one or more peaks at about 5.5, 5.7, 10.9, 16.3 and20.5 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Citrate (Form B) furthercomprises one or more peaks at about 3.4, 11.8, 14.6, 17.2 and 21.1degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 Citrate (Form B) exhibits an XRPD comprisingpeaks shown in Table 7 below:

TABLE 7 XRPD Table of Compound 1 Citrate (Form B) 2-Theta Intensity %3.4 4.8 5.5 58.1 5.7 42.3 10.9 32.1 11.4 4.3 11.8 8.9 13.6 4.5 14.6 9.714.8 3.1 16.0 2.4 16.3 100 17.2 13.3 20.5 29.8 21.1 7.5 25.6 3.2 25.9 427.3 4.4 30.9 1.6

In some embodiments, the Compound 1 Citrate (Form B) exhibits an XRPDthat is substantially similar to FIG. 18.

In some embodiments, the Compound 1 Citrate (Form B) exhibits a DSCthermogram comprising an endotherm at about 77.7° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 Citrate (Form B) exhibits aDSC thermogram comprising an endotherm at about 121.5° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 Citrate (Form B) exhibits aDSC thermogram comprising an endotherm at about 136.6° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 Citrate (Form B) exhibits aDSC thermogram that is substantially similar to FIG. 19.

In some embodiments, the Compound 1 Citrate (Form B) exhibits a TGAthermogram that is substantially similar to FIG. 19. In otherembodiments, the TGA thermogram of the Compound 1 Citrate (Form B)exhibits a weight loss of about 0.0 to 4.5% in the temperature range of25 to 120° C.

In some embodiments, the Compound 1 Citrate (Form B) exhibits a DVSisotherm plot that is substantially similar to FIG. 20. In otherembodiments, the Compound 1 Citrate (Form B) exhibits a gravimetricmoisture sorption of about 2.8% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 Citrate(Form C). In some embodiments, the Compound 1 Citrate (Form C) exhibitsan XRPD comprising one or more peaks at about 15.4, 18.7, 19.7, 20.6 and27.1 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Citrate (Form C) furthercomprises one or more peaks at about 13.5, 15.5, 16.2, 17.0 and 22.1degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 Citrate (Form C) exhibits an XRPD comprisingpeaks shown in Table 8 below.

TABLE 8 XRPD Table of Compound 1 Citrate (Form C) 2-Theta Intensity %5.1 23.1 5.6 7.8 8.2 6.5 10.3 16.4 11.3 9.3 11.9 9.8 13.5 46.3 14.5 21.615.0 40.2 15.4 82.4 15.5 66.9 16.2 49.5 17.0 49.5 17.8 42.7 18.7 78.719.7 74.8 20.6 100.0 22.1 60.4 23.4 28.7 24.1 11.8 24.7 16.6 25.8 25.326.6 23.8 27.1 83.0 27.7 11.5 28.4 21.5 29.6 5.9 30.2 13.4 31.3 7.0 31.710.3 32.2 9.7 32.8 7.1 33.7 4.0 34.2 8.2 34.8 8.5 35.6 6.2 36.6 9.3 37.07.5 37.4 8.8 38.4 7.9 39.2 8.8

In some embodiments, the Compound 1 Citrate (Form C) exhibits an XRPDthat is substantially similar to FIG. 21.

Mesylate Salt

In some embodiments, the present disclosure provides a mesylate salt ofCompound 1 (“Compound 1 Mesylate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Mesylate.

In one embodiment, the present disclosure provides Compound 1 Mesylate(Form A). In some embodiments, the Compound 1 Mesylate (Form A) exhibitsan XRPD comprising one or more peaks at about 3.6, 7.1, 14.2, 19.1 and25.9 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Mesylate (Form A) furthercomprises one or more peaks at about 7.7, 12.7, 17.8, 19.4, and 21.4degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 Mesylate (Form A) exhibits an XRPD comprisingpeaks shown in Table 9 below:

TABLE 9 XRPD Table of Compound 1 Mesylate (Form A) 2-Theta Intensity %3.6 14.5 7.1 100 7.7 9.4 12.0 3.7 12.7 8.7 13.4 3.3 14.2 24.3 17.5 2.817.8 7.4 19.1 35.4 19.4 10.1 21.4 8.1 23.6 2.2 25.4 4.2 25.9 10.3

In some embodiments, the Compound 1 Mesylate (Form A) exhibits an XRPDthat is substantially similar to FIG. 22.

In some embodiments, the Compound 1 Mesylate (Form A) exhibits a DSCthermogram comprising an endotherm at about 170.9° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 Mesylate (Form A) exhibits aDSC thermogram comprising a sharp endotherm at about 209.7° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 Mesylate (Form A)exhibits a DSC thermogram that is substantially similar to FIG. 23.

In some embodiments, the Compound 1 Mesylate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 23. In otherembodiments, the TGA thermogram of the Compound 1 Mesylate (Form A)exhibits a weight loss of 0.0 to 0.5% in the temperature range of 25 to150° C.

In some embodiments, the Compound 1 Mesylate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 24. In otherembodiments, the Compound 1 Mesylate (Form A) exhibits a gravimetricmoisture sorption of about 3.4% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 Mesylate(Form B). In some embodiments, the Compound 1 Mesylate (Form B) exhibitsan XRPD comprising one or more peaks at about 7.1, 14.3, 15.9, 21.4, and22.6 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the Compound 1 Mesylate (Form B) exhibits an XRPDcomprising peaks shown in Table 10A below:

TABLE 10A XRPD Table of Compound 1 Mesylate (Form B) 2-Theta Intensity %7.1 100 14.3 25.8 15.9 11.3 19.0 3.5 21.4 9.1 22.6 6.1

In some embodiments, the Compound 1 Mesylate (Form B) exhibits an XRPDthat is substantially similar to FIG. 25A.

In some embodiments, the present disclosure provides Compound 1 Mesylate(Form C). In some embodiments, the Compound 1 Mesylate (Form C) exhibitsan XRPD comprising one or more peaks at about 7.5, 15.0, 19.4, 22.5, and30.2 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yetanother embodiment, the Compound 1 Mesylate (Form C) exhibits an XRPDcomprising peaks shown in Table 10B below:

TABLE 10B XRPD Table of Compound 1 Mesylate (Form C) 2-Theta Intensity %7.5 100 15.0 33.1 19.4 3.1 22.5 13.3 30.2 3

In some embodiments, the Compound 1 Mesylate (Form C) exhibits an XRPDthat is substantially similar to FIG. 25B.

In one embodiment, the present disclosure provides Compound 1 Mesylate(Form D). In some embodiments, the Compound 1 Mesylate (Form D) exhibitsan XRPD comprising one or more peaks at about 7.4, 15.0, and 22.6degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 Mesylate (Form D) exhibits an XRPD comprisingpeaks shown in Table 11 below:

TABLE 11 XRPD Table of Compound 1 Mesylate (Form D) 2-Theta Intensity %7.4 100 15.0 21.1 22.6 10

In some embodiments, the Compound 1 Mesylate (Form D) exhibits an XRPDthat is substantially similar to FIG. 26.

Phosphate Salt

In some embodiments, the present disclosure provides a phosphate salt ofCompound 1 (“Compound 1 Phosphate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Phosphate.

In one embodiment, the present disclosure provides Compound 1 Phosphate(Form A). In some embodiments, the Compound 1 Phosphate (Form A)exhibits an XRPD comprising one or more peaks at about 3.3, 3.6, 5.4,9.9, and 13.1 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Phosphate (Form A)further comprises one or more peaks at about 16.1, 17.9, 20.9, 23.7, and26.4 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yetanother embodiment, the Compound 1 Phosphate (Form A) exhibits an XRPDcomprising peaks shown in Table 12 below:

TABLE 12 XRPD Table of Compound 1 Phosphate (Form A) 2-Theta Intensity %3.3 100 3.6 7.8 5.4 7.2 6.6 1.9 9.9 14.2 13.1 12.7 15.7 1.8 16.1 5.416.4 1.7 17.9 3.8 19.0 1.4 20.4 1.9 20.9 2.6 23.7 2.9 26.4 2.3 26.5 1.129.6 1.1 31.0 1.3

In some embodiments, the Compound 1 Phosphate (Form A) exhibits an XRPDthat is substantially similar to FIG. 27.

In some embodiments, the Compound 1 Phosphate (Form A) exhibits a DSCthermogram comprising a sharp endotherm at about 217.6° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 Phosphate (Form A)exhibits a DSC thermogram that is substantially similar to FIG. 28.

In some embodiments, the Compound 1 Phosphate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 28. In otherembodiments, the TGA thermogram of the Compound 1 Phosphate (Form A)exhibits a weight loss of 0.0 to 1.7% in the temperature range of 25 to204° C.

In some embodiments, the Compound 1 Phosphate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 29. In otherembodiments, the Compound 1 Phosphate (Form A) exhibits a gravimetricmoisture sorption of about 2.1% (by weight) at 80% Relative Humidity.

Tartrate Salt

In some embodiments, the present disclosure provides a tartrate salt ofCompound 1 (“Compound 1 Tartrate”). In some embodiments, the presentdisclosure provides a D(−)-tartrate salt of Compound 1 (“Compound 1D(−)-Tartrate”). In some embodiments, the present disclosure provides anL(+)-tartrate salt of Compound 1 (“Compound 1 L(+)-Tartrate”).

In some embodiments, the present disclosure provides a crystalline formof Compound 1 Tartrate. In some embodiments, the present disclosureprovides a crystalline form of Compound 1 D(−)-Tartrate. In someembodiments, the present disclosure provides a crystalline form ofCompound 1 L(+)-Tartrate.

In one embodiment, the present disclosure provides Compound 1L(+)-Tartrate (Form A). In some embodiments, the Compound 1L(+)-Tartrate (Form A) exhibits an XRPD comprising one or more peaks atabout 3.6, 4.7, 13.9, 18.6, and 22.8 degrees two-theta with the marginof error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less. In another embodiment, the XRPD of the Compound 1L(+)-Tartrate (Form A) further comprises one or more peaks at about14.6, 17.8 and 18.1 degrees two-theta with the margin of error of about±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; orless. In yet another embodiment, the Compound 1 L(+)-Tartrate (Form A)exhibits an XRPD comprising peaks shown in Table 13 below:

TABLE 13 XRPD Table of Compound 1 L(+)-Tartrate (Form A) 2-ThetaIntensity % 3.6 13.6 4.7 100 13.9 82.1 14.6 5.1 17.8 7.6 18.1 3.1 18.613 22.8 50.7

In some embodiments, the Compound 1 L(+)-Tartrate (Form A) exhibits anXRPD that is substantially similar to FIG. 30.

In some embodiments, the Compound 1 L(+)-Tartrate (Form A) exhibits aDSC thermogram comprising a sharp endotherm at about 207.6° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 L(+)-Tartrate (FormA) exhibits a DSC thermogram that is substantially similar to FIG. 31.

In some embodiments, the Compound 1 L(+)-Tartrate (Form A) exhibits aTGA thermogram that is substantially similar to FIG. 31. In otherembodiments, the TGA thermogram of the Compound 1 L(+)-Tartrate (Form A)exhibits a weight loss of 0.0 to 1.2% in the temperature range of 25 to189° C.

In some embodiments, the Compound 1 L(+)-Tartrate (Form A) exhibits aDVS isotherm plot that is substantially similar to FIG. 32. In otherembodiments, the Compound 1 L(+)-Tartrate (Form A) exhibits agravimetric moisture sorption of about 1.6% (by weight) at 80% RelativeHumidity.

In one embodiment, the present disclosure provides Compound 1L(+)-Tartrate (Form B). In some embodiments, the Compound 1L(+)-Tartrate (Form B) exhibits an XRPD comprising one or more peaks atabout 3.6, 4.6, 12.4, 13.9, and 22.7 degrees two-theta with the marginof error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less. In another embodiment, the XRPD of the Compound 1L(+)-Tartrate (Form B) further comprises one or more peaks at about14.8, 18.3 and 18.5 degrees two-theta with the margin of error of about±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; orless. In yet another embodiment, the Compound 1 L(+)-Tartrate (Form B)exhibits an XRPD comprising peaks shown in Table 14 below:

TABLE 14 XRPD Table of Compound 1 L(+)-Tartrate (Form B) 2-ThetaIntensity % 3.6 65 4.6 100 12.4 22 13.9 50.8 14.8 17.1 18.3 16.9 18.520.9 22.7 54.9

In some embodiments, the Compound 1 L(+)-Tartrate (Form B) exhibits anXRPD that is substantially similar to FIG. 33.

In some embodiments, the Compound 1 L(+)-Tartrate (Form B) exhibits aDSC thermogram comprising a sharp endotherm at about 207.3° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 L(+)-Tartrate (FormB) exhibits a DSC thermogram that is substantially similar to FIG. 34.

In some embodiments, the Compound 1 L(+)-Tartrate (Form B) exhibits aTGA thermogram that is substantially similar to FIG. 34. In otherembodiments, the TGA thermogram of the Compound 1 L(+)-Tartrate (Form B)exhibits a weight loss of 0.0 to 0.6% in the temperature range of 25 to180° C.

In some embodiments, the Compound 1 L(+)-Tartrate (Form B) exhibits aDVS isotherm plot that is substantially similar to FIG. 35. In otherembodiments, the Compound 1 L(+)-Tartrate (Form B) exhibits agravimetric moisture sorption of about 1.7% (by weight) at 80% RelativeHumidity.

Fumarate Salt

In some embodiments, the present disclosure provides a fumarate salt ofCompound 1 (“Compound 1 Fumarate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Fumarate.

In one embodiment, the present disclosure provides Compound 1 Fumarate(Form A). In some embodiments, the Compound 1 Fumarate (Form A) exhibitsan XRPD comprising one or more peaks at about 3.5 and 16.0 degreestwo-theta with the margin of error of about ±0.5; about ±0.4; about±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 Fumarate (Form A) exhibits an XRPD comprisingpeaks shown in Table 15 below:

TABLE 15 XRPD Table of Compound 1 Fumarate (Form A) 2-Theta Intensity %3.5 100 16.0 13.4

In some embodiments, the Compound 1 Fumarate (Form A) exhibits an XRPDthat is substantially similar to FIG. 36.

In some embodiments, the Compound 1 Fumarate (Form A) exhibits a DSCthermogram comprising a sharp endotherm at about 87.0° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 Fumarate (Form A) exhibitsa DSC thermogram that is substantially similar to FIG. 37.

In some embodiments, the Compound 1 Fumarate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 37. In otherembodiments, the TGA thermogram of the Compound 1 Fumarate (Form A)exhibits a weight loss of 0.0 to 0.9% in the temperature range of 25 to75° C.

In some embodiments, the present disclosure provides Compound 1 Fumarate(Form B). In some embodiments, the Compound 1 Fumarate (Form B) exhibitsan XRPD comprising one or more peaks at about 3.6, 11.0, 16.2, and 17.5degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 Fumarate (Form B) exhibits an XRPD comprisingpeaks shown in Table 16 below:

TABLE 16 XRPD Table of Compound 1 Fumarate (Form B) 2-Theta Intensity %3.6 100 11.0 12.8 16.2 23.4 17.5 13.1

In some embodiments, the Compound 1 Fumarate (Form B) exhibits an XRPDthat is substantially similar to FIG. 38.

In some embodiments, the Compound 1 Fumarate (Form B) exhibits a DSCthermogram comprising a sharp endotherm at about 89.9° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 Fumarate (Form B) exhibitsa DSC thermogram that is substantially similar to FIG. 39.

In some embodiments, the Compound 1 Fumarate (Form B) exhibits a TGAthermogram that is substantially similar to FIG. 39. In otherembodiments, the TGA thermogram of the Compound 1 Fumarate (Form B)exhibits a weight loss of 0.0 to 1.85% in the temperature range of 25 to150° C.

In some embodiments, the Compound 1 Fumarate (Form B) exhibits a DVSisotherm plot that is substantially similar to FIG. 40. In otherembodiments, the Compound 1 Fumarate (Form B) exhibits a gravimetricmoisture sorption of about 7.2% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 Fumarate(Form C). In some embodiments, the Compound 1 Fumarate (Form C) exhibitsan XRPD comprising one or more peaks at about 14.5, 15.4, 16.7, 17.6,and 28.8 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Fumarate (Form C) furthercomprises one or more peaks at about 8.4, 19.7, 20.5, 22.9, and 38.1degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 Fumarate (Form C) exhibits an XRPD comprisingpeaks shown in Table 17 below:

TABLE 17 XRPD Table of Compound 1 Fumarate (Form C) 2-Theta Intensity %8.4 26.2 9.8 8.9 12.9 10.2 14.5 46.3 15.4 100 16.7 36.6 17.6 44.4 19.721.7 20.5 27.9 21.5 12.6 22.9 20.6 23.3 8.2 25.2 15.8 25.7 12.1 27.414.5 28.8 41.6 38.1 28.8

In some embodiments, the Compound 1 Fumarate (Form C) exhibits an XRPDthat is substantially similar to FIG. 41.

In one embodiment, the present disclosure provides Compound 1 Fumarate(Form D). In some embodiments, the Compound 1 Fumarate (Form D) exhibitsan XRPD comprising one or more peaks at about 5.2, 12.2, 15.2, 15.5, and19.9 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Fumarate (Form D) furthercomprises one or more peaks at about 10.4, 13.6, 14.2, 21.2, and 22.3degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In yet anotherembodiment, the Compound 1 Fumarate (Form D) exhibits an XRPD comprisingpeaks shown in Table 18 below:

TABLE 18 XRPD Table of Compound 1 Fumarate (Form D) 2-Theta Intensity %5.2 29.5 10.4 23.5 12.2 100 13.6 27.9 14.2 28.8 15.2 42 15.5 40 16.519.6 16.9 13.5 17.2 9.6 19.1 11 19.9 40.9 20.5 19.2 21.2 27.9 22.3 21.222.9 17.1 23.5 17.4 24.0 21.2 24.6 13.5 26.2 18.5 26.9 14.4 28.9 15.1

In some embodiments, the Compound 1 Fumarate (Form D) exhibits an XRPDthat is substantially similar to FIG. 42.

Tosylate Salt

In some embodiments, the present disclosure provides a tosylate salt ofCompound 1 (“Compound 1 Tosylate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Tosylate.

In one embodiment, the present disclosure provides Compound 1 Tosylate(Form A). In some embodiments, the Compound 1 Tosylate (Form A) exhibitsan XRPD comprising one or more peaks at about 3.4, 9.8, 10.3, 12.5, and15.3 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Tosylate (Form A) furthercomprises one or more peaks at about 17.4, 17.9, 19.6, 23.2 and 26.0degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In yet another embodiment, the Compound 1 Tosylate (Form A) exhibits anXRPD comprising peaks shown in Table 19 below:

TABLE 19 XRPD Table of Compound 1 Tosylate (Form A) 2-Theta Intensity %3.4 100 9.8 3.1 10.3 3 12.5 7 15.3 6.3 15.8 1.1 16.5 0.9 16.9 1.1 17.42.2 17.9 1.8 19.0 1.4 19.6 2.6 20.7 1.3 21.4 1.5 23.2 1.7 23.6 1.1 26.01.9 27.2 1.1 27.5 1.3 28.7 1 29.6 0.7 30.7 0.9

In some embodiments, the Compound 1 Tosylate (Form A) exhibits an XRPDthat is substantially similar to FIG. 43.

In some embodiments, the Compound 1 Tosylate (Form A) exhibits a DSCthermogram comprising a sharp endotherm at about 186.2° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 Tosylate (Form A)exhibits a DSC thermogram that is substantially similar to FIG. 44.

In some embodiments, the Compound 1 Tosylate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 44. In otherembodiments, the TGA thermogram of the Compound 1 Tosylate (Form A)exhibits a weight loss of 0.0 to 0.9% in the temperature range of 25 to175° C.

In some embodiments, the Compound 1 Tosylate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 45. In otherembodiments, the Compound 1 Tosylate (Form A) exhibits a gravimetricmoisture sorption of about 1.5% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 Tosylate(Form B). In some embodiments, the Compound 1 Tosylate (Form B) exhibitsan XRPD comprising one or more peaks at about 10.0, 15.2, 15.5, 17.2,and 19.4 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Tosylate (Form B) furthercomprises one or more peaks at about 10.3, 16.7, 19.1, 20.1 and 20.8degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In yet another embodiment, the Compound 1 Tosylate (Form B) exhibits anXRPD comprising peaks shown in Table 20 below:

TABLE 20 XRPD Table of Compound 1 Tosylate (Form B) 2-Theta Intensity %6.8 16.7 9.1 24.4 10.0 100 10.3 39.9 11.0 12.8 11.9 23.8 12.2 25.9 13.015.5 13.5 19.3 15.2 58.3 15.5 65.5 16.2 27.1 16.7 35.1 17.2 47.9 18.523.2 19.1 29.2 19.4 41.7 19.8 28.0 20.1 32.1 20.8 40.2 21.7 25.6 22.225.3 23.2 21.7 24.4 20.5 25.6 26.8 26.2 26.8 27.2 18.5 28.4 17.9 29.012.8

In some embodiments, the Compound 1 Tosylate (Form B) exhibits an XRPDthat is substantially similar to FIG. 46.

In one embodiment, the present disclosure provides Compound 1 Tosylate(Form C). In some embodiments, the Compound 1 Tosylate (Form C) exhibitsan XRPD comprising one or more peaks at about 7.4, 10.2, 12.5, 18.3, and19.7 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Tosylate (Form C) furthercomprises one or more peaks at about 9.8, 14.7, 16.6, 17.8, and 23.2degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In yet another embodiment, the Compound 1 Tosylate (Form C) exhibits anXRPD comprising peaks shown in Table 21 below:

TABLE 21 XRPD Table of Compound 1 Tosylate (Form C) 2-Theta Intensity %7.4 70 9.8 28.2 10.2 46.9 10.8 16.4 11.4 21.8 12.5 100 13.1 15.6 13.817.1 14.7 34.2 15.3 16.7 16.6 40.2 16.9 16 17.4 16.2 17.8 41.6 18.3 65.119.7 85.6 20.3 8 20.7 14.2 21.1 18.9 21.4 16 22.2 26.7 22.8 9.3 23.246.4 23.6 14.9 24.2 11.8 24.7 16.9 25.9 21.6 27.2 11.3 27.5 20.9 28.617.8 30.5 16.2 30.8 13.8 31.2 12.4 37.8 11.1

In some embodiments, the Compound 1 Tosylate (Form C) exhibits an XRPDthat is substantially similar to FIG. 47.

Glucuronate Salt

In some embodiments, the present disclosure provides a glucuronate saltof Compound 1 (“Compound 1 Glucuronate”). In some embodiments, thepresent disclosure provides a D-glucuronate salt of Compound 1(“Compound 1 D-Glucuronate”). In some embodiments, the presentdisclosure provides L-glucuronate salt of Compound 1 (“Compound 1L-Glucuronate”).

In some embodiments, the present disclosure provides a crystalline formof Compound 1 Glucuronate. In some embodiments, the present disclosureprovides a crystalline form of Compound 1 D-Glucuronate. In someembodiments, the present disclosure provides a crystalline form ofCompound 1 L-Glucuronate.

In one embodiment, the present disclosure provides Compound 1D-Glucuronate (Form A). In some embodiments, the Compound 1D-Glucuronate (Form A) exhibits an XRPD comprising one or more peaks atabout 4.3, 12.9, 16.8, 20.2 and 20.9 degrees two-theta with the marginof error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less. In another embodiment, the XRPD of the Compound 1D-Glucuronate (Form A) further comprises one or more peaks at about 3.3,14.7, 17.3, 21.6, and 24.8 degrees two-theta with the margin of error ofabout ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05;or less.

In yet another embodiment, the Compound 1 D-Glucuronate (Form A)exhibits an XRPD comprising peaks shown in Table 22 below:

TABLE 22 XRPD Table of Compound 1 D-Glucuronate (Form A) 2-ThetaIntensity % 3.3 30.3 4.3 100 11.6 8.8 12.9 51.1 13.8 11.1 14.7 24.3 15.08.3 15.4 18.7 16.8 62.1 17.3 38.5 20.2 49.3 20.9 99.8 21.6 20.9 22.4 824.2 20 24.8 20.5 25.7 5.7 28.2 9.1 28.8 5.7 30.8 9.1 32.5 11.3

In some embodiments, the Compound 1 D-Glucuronate (Form A) exhibits anXRPD that is substantially similar to FIG. 48.

In some embodiments, the Compound 1 D-Glucuronate (Form A) exhibits aDSC thermogram comprising a endotherm at about 116.2° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In another embodiment, the Compound 1 D-Glucuronate (Form A)exhibits a DSC thermogram comprising a endotherm at about 139.3° C. withthe error of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0;about ±0.5; or less. In some embodiments, the Compound 1 D-Glucuronate(Form A) exhibits a DSC thermogram that is substantially similar to FIG.49.

In some embodiments, the Compound 1 D-Glucuronate (Form A) exhibits aTGA thermogram that is substantially similar to FIG. 49. In otherembodiments, the TGA thermogram of the Compound 1 D-Glucuronate (Form A)exhibits a weight loss of 0.0 to 3.0% in the temperature range of 25 to120° C.

In some embodiments, the Compound 1 D-Glucuronate (Form A) exhibits aDVS isotherm plot that is substantially similar to FIG. 50. In otherembodiments, the Compound 1 D-Glucuronate (Form A) exhibits agravimetric moisture sorption of about 1.4% (by weight) at 80% RelativeHumidity.

In one embodiment, the present disclosure provides Compound 1D-Glucuronate (Form B). In some embodiments, the Compound 1D-Glucuronate (Form B) exhibits an XRPD comprising one or more peaks atabout 14.7, 16.7, 17.0, 20.0 and 20.4 degrees two-theta with the marginof error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less. In another embodiment, the XRPD of the Compound 1D-Glucuronate (Form B) further comprises one or more peaks at about 8.5,15.0, 19.5, 22.5 and 24.3 degrees two-theta with the margin of error ofabout ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05;or less.

In yet another embodiment, the Compound 1 D-Glucuronate (Form B)exhibits an XRPD comprising peaks shown in Table 23 below:

TABLE 23 XRPD Table of Compound 1 D-Glucuronate (Form B) 2-ThetaIntensity % 8.5 16.1 11.7 7.1 14.7 100 15.0 24.8 16.7 45.2 17.0 67.719.1 4.7 19.5 18.7 20.0 32.9 20.4 42.3 21.7 11.1 22.5 15.6 22.9 8.5 24.318 24.8 7.4 25.4 11.2 25.6 14.2 26.2 14.2 28.0 4.1 28.8 3.8 30.1 6.230.6 13.6 35.2 9.1 35.8 6.5 38.3 5.1 39.2 5

In some embodiments, the Compound 1 D-Glucuronate (Form B) exhibits anXRPD that is substantially similar to FIG. 51.

Ethanesulfonate Salt

In some embodiments, the present disclosure provides an ethanesulfonatesalt of Compound 1 (“Compound 1 Ethanesulfonate”). In some embodiments,the present disclosure provides a crystalline form of Compound 1Ethanesulfonate.

In one embodiment, the present disclosure provides Compound 1Ethanesulfonate (Form A). In some embodiments, the Compound 1Ethanesulfonate (Form A) exhibits an XRPD comprising one or more peaksat about 3.4, 3.7, 7.6, 15.3, and 23.0 degrees two-theta with the marginof error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less. In another embodiment, the XRPD of the Compound 1Ethanesulfonate (Form A) further comprises one or more peaks at about23.3 and 30.8 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In yet another embodiment, the Compound 1 Ethanesulfonate (Form A)exhibits an XRPD comprising peaks shown in Table 24 below:

TABLE 24 XRPD Table of Compound 1 Ethanesulfonate (Form A) 2-ThetaIntensity % 3.4 22.4 3.7 11.7 7.6 100 15.3 70.3 23.0 21.6 23.3 1.6 30.84.3

In some embodiments, the Compound 1 Ethanesulfonate (Form A) exhibits anXRPD that is substantially similar to FIG. 52.

In some embodiments, the Compound 1 Ethanesulfonate (Form A) exhibits aDSC thermogram comprising a endotherm at about 177.9° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In another embodiment, the Compound 1 Ethanesulfonate (Form A)exhibits a DSC thermogram comprising a endotherm at about 207.0° C. withthe error of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0;about ±0.5; or less. In some embodiments, the Compound 1 Ethanesulfonate(Form A) exhibits a DSC thermogram that is substantially similar to FIG.53.

In some embodiments, the Compound 1 Ethanesulfonate (Form A) exhibits aTGA thermogram that is substantially similar to FIG. 53. In otherembodiments, the TGA thermogram of the Compound 1 Ethanesulfonate (FormA) exhibits a weight loss of 0.0 to 2.9% in the temperature range of 25to 180° C.

In some embodiments, the Compound 1 Ethanesulfonate (Form A) exhibits aDVS isotherm plot that is substantially similar to FIG. 54. In otherembodiments, the Compound 1 Ethanesulfonate (Form A) exhibits agravimetric moisture sorption of about 1.4% (by weight) at 80% RelativeHumidity.

Sulfate Salt

In some embodiments, the present disclosure provides a sulfate salt ofCompound 1 (“Compound 1 Sulfate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Sulfate.

In one embodiment, the present disclosure provides Compound 1 Sulfate(Form A). In some embodiments, the Compound 1 Sulfate (Form A) exhibitsan XRPD comprising one or more peaks at about 3.6, 5.2, 7.8, 8.1, and15.1 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Sulfate (Form A) furthercomprises one or more peaks at about 14.7, 17.4, 18.2, 18.4, and 19.7degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In someembodiments, the Compound 1 Sulfate (Form A) exhibits an XRPD comprisingpeaks shown in Table 25 below:

TABLE 25 XRPD Table of Compound 1 Sulfate (Form A) 2-Theta Intensity %3.6 100 5.2 39 7.8 50 8.1 16.4 14.2 9 14.7 9.6 15.1 13.6 17.4 10.3 18.210.6 18.4 9.4 19.7 11.3 20.8 9 21.6 8.2 24.0 8.8

In some embodiments, the Compound 1 Sulfate (Form A) exhibits an XRPDthat is substantially similar to FIG. 55.

In some embodiments, the Compound 1 Sulfate (Form A) exhibits a DSCthermogram comprising a endotherm at about 167.1° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 Sulfate (Form A) exhibits aDSC thermogram that is substantially similar to FIG. 56.

In some embodiments, the Compound 1 Sulfate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 56. In otherembodiments, the TGA thermogram of the Compound 1 Sulfate (Form A)exhibits a weight loss of 0.0 to 1.0% in the temperature range of 25 to120° C.

In some embodiments, the Compound 1 Sulfate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 57. In otherembodiments, the Compound 1 Sulfate (Form A) exhibits a gravimetricmoisture sorption of about 6.2% (by weight) at 80% Relative Humidity.

Ascorbate Salt

In some embodiments, the present disclosure provides an ascorbate saltof Compound 1 (“Compound 1 Ascorbate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Ascorbate.

In one embodiment, the present disclosure provides Compound 1 Ascorbate(Form A). In some embodiments, the Compound 1 Ascorbate (Form A)exhibits an XRPD comprising one or more peaks at about 3.6, 5.6, 16.6,19.6, and 19.8 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Ascorbate (Form A)further comprises one or more peaks at about 11.5, 11.9, 21.6, 24.1, and24.5 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Ascorbate (Form A) exhibits an XRPDcomprising peaks shown in Table 26 below:

TABLE 26 XRPD Table of Compound 1 Ascorbate (Form A) 2-Theta Intensity %3.6 28.5 5.6 31.7 9.6 9.7 11.0 8.8 11.5 13.8 11.9 13.3 14.5 12.9 16.6100 18.9 6.3 19.6 31.9 19.8 22.5 21.6 14.7 22.1 5.1 22.9 6 23.2 10.624.1 15.1 24.5 21.1

In some embodiments, the Compound 1 Ascorbate (Form A) exhibits an XRPDthat is substantially similar to FIG. 58.

In some embodiments, the Compound 1 Ascorbate (Form A) exhibits a DSCthermogram comprising a endotherm at about 46.3° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 Ascorbate (Form A) exhibits aDSC thermogram comprising a endotherm at about 124.3° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 Ascorbate (Form A) exhibitsa DSC thermogram that is substantially similar to FIG. 59.

In some embodiments, the Compound 1 Ascorbate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 59. In otherembodiments, the TGA thermogram of the Compound 1 Ascorbate (Form A)exhibits a weight loss of 0.0 to 5.6% in the temperature range of 25 to120° C.

In some embodiments, the Compound 1 Ascorbate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 60. In otherembodiments, the Compound 1 Ascorbate (Form A) exhibits a gravimetricmoisture sorption of about 5.7% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 Ascorbate(Form B). In some embodiments, the Compound 1 Ascorbate (Form B)exhibits an XRPD comprising one or more peaks at about 5.5, 16.6, 19.7,20.1, and 28.3 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Ascorbate (Form B)further comprises one or more peaks at about 14.7 and 23.6 degreestwo-theta with the margin of error of about ±0.5; about ±0.4; about±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Ascorbate (Form B) exhibits an XRPDcomprising peaks shown in Table 27 below:

TABLE 27 XRPD Table of Compound 1 Ascorbate (Form B) 2-Theta Intensity %5.5 74.9 14.7 21.2 16.6 100 19.7 29.6 20.1 38 23.6 22.9 28.3 39.7

In some embodiments, the Compound 1 Ascorbate (Form B) exhibits an XRPDthat is substantially similar to FIG. 61.

Napadisylate Salt

In some embodiments, the present disclosure provides a napadisylate saltof Compound 1 (“Compound 1 Napadisylate”). In some embodiments, thepresent disclosure provides a crystalline form of Compound 1Napadisylate.

In one embodiment, the present disclosure provides Compound 1Napadisylate (Form A). In some embodiments, the Compound 1 Napadisylate(Form A) exhibits an XRPD comprising one or more peaks at about 3.3,9.4, 14.2, 16.4, and 17.8 degrees two-theta with the margin of error ofabout ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05;or less. In another embodiment, the XRPD of the Compound 1 Napadisylate(Form A) further comprises one or more peaks at about 9.7, 17.3, 20.3,24.4, and 26.1 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Insome embodiments, the Compound 1 Napadisylate (Form A) exhibits an XRPDcomprising peaks shown in Table 28 below:

TABLE 28 XRPD Table of Compound 1 Napadisylate (Form A) 2-ThetaIntensity % 3.3 70.6 3.6 18.5 4.7 15.3 7.1 7.7 9.4 38.1 9.7 35.7 14.2 5216.4 100 17.3 23.3 17.8 77.6 19.6 22.9 20.3 24.5 20.8 19.9 22.1 12.622.6 6.6 23.0 17.3 24.4 23.7 25.5 6.2 26.1 37.4 27.3 19.7 28.3 7.6

In some embodiments, the Compound 1 Napadisylate (Form A) exhibits anXRPD that is substantially similar to FIG. 62.

In some embodiments, the Compound 1 Napadisylate (Form A) exhibits a DSCthermogram comprising a endotherm at about 41.7° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 Napadisylate (Form A) exhibitsa DSC thermogram that is substantially similar to FIG. 63.

In some embodiments, the Compound 1 Napadisylate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 63. In otherembodiments, the TGA thermogram of the Compound 1 Napadisylate (Form A)exhibits a weight loss of 0.0 to 0.7% in the temperature range of 25 to120° C.

In some embodiments, the Compound 1 Napadisylate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 64. In otherembodiments, the Compound 1 Napadisylate exhibits a gravimetric moisturesorption of about 3.1% (by weight) at 80% Relative Humidity.

In some embodiments, the present disclosure provides Compound 1Napadisylate (Form B). In some embodiments, the Compound 1 Napadisylate(Form B) exhibits an XRPD comprising one or more peaks at about 6.0,14.2, 18.1, 19.0, and 20.3 degrees two-theta with the margin of error ofabout ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05;or less. In another embodiment, the XRPD of the Compound 1 Napadisylate(Form B) further comprises one or more peaks at about 12.0, 16.9, 18.4,19.4, and 24.1 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Napadisylate (Form B) exhibits anXRPD comprising peaks shown in Table 29 below:

TABLE 29 XRPD Table of Compound 1 Napadisylate (Form B) 2-ThetaIntensity % 6.0 100 12.0 18.2 13.3 14.8 13.5 12.4 14.2 33.8 16.9 23.618.1 51.1 18.4 22.9 19.0 26.3 19.4 17 20.3 39.9 21.7 10.5 24.1 22.4 25.811.2

In some embodiments, the Compound 1 Napadisylate (Form B) exhibits anXRPD that is substantially similar to FIG. 65.

Malonate Salt

In some embodiments, the present disclosure provides a malonate salt ofCompound 1 (“Compound 1 Malonate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Malonate.

In one embodiment, the present disclosure provides Compound 1 Malonate(Form A). In some embodiments, the Compound 1 Malonate (Form A) exhibitsan XRPD comprising one or more peaks at about 15.1, 18.0, 18.8, 23.4,and 23.8 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Malonate (Form A) furthercomprises one or more peaks at about 3.6, 13.8, 15.6, 21.4, and 27.6degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Malonate (Form A) exhibits an XRPDcomprising peaks shown in Table 30 below:

TABLE 30 XRPD Table of Compound 1 Malonate (Form A) 2-Theta Intensity %3.6 26.7 10.9 13.6 11.7 6.7 12.1 17.6 13.8 25 14.6 15 15.1 60.1 15.629.2 16.7 7.4 18.0 100 18.8 85.6 20.6 18.3 21.4 24.8 21.7 24.1 23.1 17.823.4 43.3 23.8 56.3 25.0 8.2 25.6 8.3 27.6 37.3 29.4 17.5

In some embodiments, the Compound 1 Malonate (Form A) exhibits an XRPDthat is substantially similar to FIG. 66.

In some embodiments, the Compound 1 Malonate (Form A) exhibits a DSCthermogram comprising a endotherm at about 36.9° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 Malonate (Form A) exhibits aDSC thermogram comprising a endotherm at about 124.6° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 Malonate (Form A) exhibitsa DSC thermogram that is substantially similar to FIG. 67.

In some embodiments, the Compound 1 Malonate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 67. In otherembodiments, the TGA thermogram of the Compound 1 Malonate (Form A)exhibits a weight loss of 0.0 to 1.9% in the temperature range of 25 to120° C.

Besylate Salt

In some embodiments, the present disclosure provides a besylate salt ofCompound 1 (“Compound 1 Besylate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Besylate.

In one embodiment, the present disclosure provides Compound 1 Besylate(Form A). In some embodiments, the Compound 1 Besylate (Form A) exhibitsan XRPD comprising one or more peaks at about 14.7, 15.8, 22.1, 23.2,and 26.6 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Besylate (Form A) furthercomprises one or more peaks at about 3.7, 16.2, 17.8, 19.5, and 30.4degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Besylate (Form A) exhibits an XRPDcomprising peaks shown in Table 31 below:

TABLE 31 XRPD Table of Compound 1 Besylate (Form A) 2-Theta Intensity %3.3 21.9 3.7 7 7.4 100 14.7 41.9 15.8 3.5 16.2 19.3 17.2 5.7 17.8 9.119.5 9.3 22.1 21.4 23.2 20.6 26.6 3.8 29.6 3.6 30.4 7.3

In some embodiments, the Compound 1 Besylate (Form A) exhibits an XRPDthat is substantially similar to FIG. 68.

In some embodiments, the Compound 1 Besylate (Form A) exhibits a DSCthermogram comprising a sharp endotherm at about 194.2° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 Besylate (Form A)exhibits a DSC thermogram that is substantially similar to FIG. 69.

In some embodiments, the Compound 1 Besylate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 69. In otherembodiments, the TGA thermogram of the Compound 1 Besylate (Form A)exhibits a weight loss of 0.0 to 3.3% in the temperature range of 25 to120° C.

In some embodiments, the Compound 1 Besylate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 70. In otherembodiments, the Compound 1 Besylate (Form A) exhibits a gravimetricmoisture sorption of about 4.0% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 Besylate(Form B).

In some embodiments, the Compound 1 Besylate (Form B) exhibits an XRPDcomprising one or more peaks at about 7.3, 14.7, 22.1, 23.2, and 29.6degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In anotherembodiment, the XRPD of the Compound 1 Besylate (Form B) furthercomprises one or more peaks at about 7.9, 16.2, 16.4, 17.2, and 30.4degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Besylate (Form B) exhibits an XRPDcomprising peaks shown in Table 32 below:

TABLE 32 XRPD Table of Compound 1 Besylate (Form B) 2-Theta Intensity %7.3 100 7.9 0.5 14.7 51.7 16.2 3.4 16.4 3.0 17.2 2.7 22.1 24.5 23.2 7.729.6 4.4 30.4 2.7

In some embodiments, the Compound 1 Besylate (Form B) exhibits an XRPDthat is substantially similar to FIG. 71.

Isethionate Salt

In some embodiments, the present disclosure provides an isethionate saltof Compound 1 (“Compound 1 Isethionate”). In some embodiments, thepresent disclosure provides a crystalline form of Compound 1Isethionate.

In one embodiment, the present disclosure provides Compound 1Isethionate (Form A).

In some embodiments, the Compound 1 Isethionate (Form A) exhibits anXRPD comprising one or more peaks at about 5.6, 16.7, 16.9, 18, and 20.9degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. In anotherembodiment, the XRPD of the Compound 1 Isethionate (Form A) furthercomprises one or more peaks at about 3.7, 15.7, 16.2, 20.7, and 25.1degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Isethionate (Form A) exhibits anXRPD comprising peaks shown in Table 33 below:

TABLE 33 XRPD Table of Compound 1 Isethionate (Form A) 2-Theta Intensity% 3.7 23.7 5.6 26.4 9.6 5 10.0 10.8 11.2 6.8 13.1 17 14.1 9.8 14.6 7.714.7 7 15.7 24.8 16.2 18.5 16.7 100 16.9 46.9 18.1 26.1 19.2 10.1 19.56.6 20.1 7.1 20.3 12.5 20.7 19.2 20.9 45.1 22.4 7.2 25.1 23.1 25.6 8.726.1 7.9 27.7 12.8 28.0 7.5

In some embodiments, the Compound 1 Isethionate (Form A) exhibits anXRPD that is substantially similar to FIG. 72.

In some embodiments, the Compound 1 Isethionate (Form A) exhibits a DSCthermogram comprising a sharp endotherm at about 153.3° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 Isethionate (Form A)exhibits a DSC thermogram that is substantially similar to FIG. 73.

In some embodiments, the Compound 1 Isethionate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 73. In otherembodiments, the TGA thermogram of the Compound 1 Isethionate (Form A)exhibits a weight loss of 0.0 to 0.0% in the temperature range of 25 to120° C.

In some embodiments, the Compound 1 Isethionate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 74. In otherembodiments, the Compound 1 Isethionate (Form A) exhibits a gravimetricmoisture sorption of about 4.9% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1Isethionate (Form B). In some embodiments, the Compound 1 Isethionate(Form B) exhibits an XRPD comprising one or more peaks at about 14.5,15.8, 17.9, 18.1, and 18.6 degrees two-theta with the margin of error ofabout ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05;or less. In another embodiment, the XRPD of the Compound 1 Isethionate(Form B) further comprises one or more peaks at about 11.4, 13.1, 14.2,15.0, and 17.0 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Isethionate (Form B) exhibits anXRPD comprising peaks shown in Table 34 below:

TABLE 34 XRPD Table of Compound 1 Isethionate (Form B) 2-Theta Intensity% 8.5 15.7 11.4 27.1 13.1 29.2 14.2 26.5 14.5 71.4 15.0 23.4 15.8 30.517.0 24.0 17.9 100 18.1 54.8 18.6 75.1 19.5 14.8 22.1 14.8 24.2 16.927.2 15.4 27.5 10.5

In some embodiments, the Compound 1 Isethionate (Form B) exhibits anXRPD that is substantially similar to FIG. 75.

Gentisate Salt

In some embodiments, the present disclosure provides a gentisate salt ofCompound 1 (“Compound 1 Gentisate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Gentisate.

In one embodiment, the present disclosure provides Compound 1 Gentisate(Form A). In some embodiments, the Compound 1 Gentisate (Form A)exhibits an XRPD comprising one or more peaks at about 3.4, 3.6, 7.0,14.6, and 21.4 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Gentisate (Form A)further comprises one or more peaks at about 16.0, 18.0, 18.5, 19.5, and21.1 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Gentisate (Form A) exhibits an XRPDcomprising peaks shown in Table 35 below:

TABLE 35 XRPD Table of Compound 1 Gentisate (Form A) 2-Theta Intensity %3.4 100 3.6 54.6 5.3 10.1 7.0 88.3 7.6 5.8 8.1 12.3 9.0 8.2 10.9 20 14.018.5 14.6 42.3 16.0 30.1 16.3 25.7 18.0 40.3 18.5 28.1 19.5 31.7 19.811.8 21.1 39.1 21.4 48 21.8 6.8 22.8 22.4 23.3 7.8

In some embodiments, the Compound 1 Gentisate (Form A) exhibits an XRPDthat is substantially similar to FIG. 76.

In some embodiments, the Compound 1 Gentisate (Form A) exhibits a DSCthermogram comprising a sharp endotherm at about 117.7° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 Gentisate (Form A)exhibits a DSC thermogram that is substantially similar to FIG. 77.

In some embodiments, the Compound 1 Gentisate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 77. In otherembodiments, the TGA thermogram of the Compound 1 Gentisate (Form A)exhibits a weight loss of 0.0 to 9.0% in the temperature range of 25 to200° C.

In some embodiments, the Compound 1 Gentisate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 78. In otherembodiments, the Compound 1 Gentisate (Form A) exhibits a gravimetricmoisture sorption of about 3.1% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 Gentisate(Form B). In some embodiments, the Compound 1 Gentisate (Form B)exhibits an XRPD comprising one or more peaks at about 5.5, 10.9, 16.4,21.9, and 22.8 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Gentisate (Form B)further comprises one or more peaks at about 9.2, 13.0, 17.2, 18.7, and27.8 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Gentisate (Form B) exhibits an XRPDcomprising peaks shown in Table 36 below:

TABLE 36 XRPD Table of Compound 1 Gentisate (Form B) 2-Theta Intensity %5.5 100 9.2 12.5 10.9 25.5 11.6 2.7 13.0 5.4 14.8 3.1 16.4 70.6 17.211.2 18.3 5.2 18.7 11.2 20.5 1.7 21.9 12.8 22.8 20.9 23.2 4.5 23.8 2.626.0 1.5 26.2 2.1 27.2 2.7 27.5 2.6 27.8 5.6 28.7 1.8 28.9 2.3

In some embodiments, the Compound 1 Gentisate (Form B) exhibits an XRPDthat is substantially similar to FIG. 79.

In one embodiment, the present disclosure provides Compound 1 Gentisate(Form C). In some embodiments, the Compound 1 Gentisate (Form C)exhibits an XRPD comprising one or more peaks at about 5.3, 15.2, 15.9,21.4, and 26.6 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Gentisate (Form C)further comprises one or more peaks at about 7.6, 10.6, 13.8, 16.9, and19.8 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Gentisate (Form C) exhibits an XRPDcomprising peaks shown in Table 37 below:

TABLE 37 XRPD Table of Compound 1 Gentisate (Form C) 2-Theta Intensity %5.3 71.5 7.6 39.3 10.6 28.0 12.1 16.7 13.8 37.8 15.2 63.5 15.9 100 16.219.8 16.9 24.4 19.8 27.7 21.4 78.3 22.7 4.0 23.7 4.6 24.0 7.3 26.6 49.628.9 7.4

In some embodiments, the Compound 1 Gentisate (Form C) exhibits an XRPDthat is substantially similar to FIG. 80.

1-Hydroxy-2-napthoate Salt

In some embodiments, the present disclosure provides a1-hydroxy-2-napthoate salt of Compound 1 (“Compound 11-Hydroxy-2-napthoate”). In some embodiments, the present disclosureprovides a crystalline form of Compound 1 1-Hydroxy-2-napthoate.

In one embodiment, the present disclosure provides Compound 11-Hydroxy-2-napthoate (Form A). In some embodiments, the Compound 11-Hydroxy-2-napthoate (Form A) exhibits an XRPD comprising one or morepeaks at about 3.2, 6.2, 13.8, 21.2, and 21.6 degrees two-theta with themargin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about±0.1; about ±0.05; or less. In another embodiment, the XRPD of theCompound 1 1-Hydroxy-2-napthoate (Form A) further comprises one or morepeaks at about 13.4, 16.2, 19.9, 20.2, and 24.7 degrees two-theta withthe margin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2;about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form A)exhibits an XRPD comprising peaks shown in Table 38 below:

TABLE 38 XRPD Table of Compound 1 1-Hydroxy-2-napthoate (Form A) 2-ThetaIntensity % 3.2 100 6.2 17.9 10.6 7.3 10.8 8.9 13.4 16.2 13.8 21.9 16.214.2 16.7 5.5 18.2 7.1 19.9 14.7 20.2 10.3 21.2 29.4 21.6 22.6 22.8 5.824.7 9.6

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form A)exhibits an XRPD that is substantially similar to FIG. 81.

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form A)exhibits a DSC thermogram comprising a endotherm at about 57.7° C. withthe error of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0;about ±0.5; or less. In some embodiments, the Compound 11-Hydroxy-2-napthoate (Form A) exhibits a DSC thermogram comprising aendotherm at about 79.1° C. with the error of margin of about ±2.5;about ±2.0; about ±1.5; about ±1.0; about ±0.5; or less. In someembodiments, the Compound 1 1-Hydroxy-2-napthoate (Form A) exhibits aDSC thermogram comprising a endotherm at about 116.1° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (FormA) exhibits a DSC thermogram comprising a endotherm at about 164.7° C.with the error of margin of about ±2.5; about ±2.0; about ±1.5; about±1.0; about ±0.5; or less. In some embodiments, the Compound 11-Hydroxy-2-napthoate (Form A) exhibits a DSC thermogram that issubstantially similar to FIG. 82.

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form A)exhibits a TGA thermogram that is substantially similar to FIG. 82. Inother embodiments, the TGA thermogram of the Compound 11-Hydroxy-2-napthoate (Form A) exhibits a weight loss of 0.0 to 3.6% inthe temperature range of 25 to 120° C.

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form A)exhibits a DVS isotherm plot that is substantially similar to FIG. 83.In other embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form A)exhibits a gravimetric moisture sorption of about 4.6% (by weight) at80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 11-Hydroxy-2-napthoate (Form B). In some embodiments, the Compound 11-Hydroxy-2-napthoate (Form B) exhibits an XRPD comprising one or morepeaks at about 8.0, 8.6, 13.5, 13.8, and 20.6 degrees two-theta with themargin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about±0.1; about ±0.05; or less. In another embodiment, the XRPD of theCompound 1 1-Hydroxy-2-napthoate (Form B) further comprises one or morepeaks at about 14.4, 15.2, 16.1, 21.4, and 23.8 degrees two-theta withthe margin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2;about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form B)exhibits an XRPD comprising peaks shown in Table 39 below:

TABLE 39 XRPD Table of Compound 1 1-Hydroxy-2-napthoate (Form B) 2-ThetaIntensity % 8.0 34.8 8.6 37.1 10.6 6.9 11.8 15 13.5 57.4 13.8 37 14.420.9 15.2 15.9 15.6 11.1 16.1 17.7 16.5 7.3 17.2 7.7 18.3 9.5 19.3 8.519.6 7 20.0 6.8 20.6 100 21.4 26.6 22.4 8.9 23.3 5.5 23.8 19.9 24.9 725.1 6.3 26.0 4.4 26.4 4.6 27.0 10.7 27.5 8.4 27.9 6.6 28.3 14.4 28.75.5 34.3 4.7 36.4 4.2 38.3 4.6 38.6 3.7

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form B)exhibits an XRPD that is substantially similar to FIG. 84.

In one embodiment, the present disclosure provides Compound 11-Hydroxy-2-napthoate (Form C). In some embodiments, the Compound 11-Hydroxy-2-napthoate (Form C) exhibits an XRPD comprising one or morepeaks at about 8.5, 13.7, 14.2, 17.3, and 21.4 degrees two-theta withthe margin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2;about ±0.1; about ±0.05; or less. In another embodiment, the XRPD of theCompound 1 1-Hydroxy-2-napthoate (Form C) further comprises one or morepeaks at about 7.7, 15.4, 20.2, 20.6, and 21.1 degrees two-theta withthe margin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2;about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form C)exhibits an XRPD comprising peaks shown in Table 40 below:

TABLE 40 XRPD Table of Compound 1 1-Hydroxy-2-napthoate (Form C) 2-ThetaIntensity % 5.0 20.3 5.4 22.3 7.7 43.6 8.0 27.8 8.5 77.3 10.5 17.5 10.718.6 11.0 15.1 12.5 25.1 13.7 80.1 14.2 100 15.4 62.2 16.1 22.7 17.372.9 17.6 28.5 17.8 18.2 18.2 22.7 19.2 13.4 20.2 35.1 20.6 42.3 20.829.2 21.1 46 21.4 70.4 27.5 15.5

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form C)exhibits an XRPD that is substantially similar to FIG. 85.

In one embodiment, the present disclosure provides Compound 11-Hydroxy-2-napthoate (Form D). In some embodiments, the Compound 11-Hydroxy-2-napthoate (Form D) exhibits an XRPD comprising one or morepeaks at about 10.4, 12.9, 13.5, 20.4, and 20.9 degrees two-theta withthe margin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2;about ±0.1; about ±0.05; or less. In another embodiment, the XRPD of theCompound 1 1-Hydroxy-2-napthoate (Form D) further comprises one or morepeaks at about 6.3, 9.1, 11.2, 13.2, and 19.9 degrees two-theta with themargin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form D)exhibits an XRPD comprising peaks shown in Table 41 below:

TABLE 41 XRPD Table of Compound 1 1-Hydroxy-2-napthoate (Form D) 2-ThetaIntensity % 6.3 20.2 9.1 14.6 10.4 46.3 11.2 16.5 12.1 11.3 12.9 29.913.2 22.5 13.5 40.5 19.5 14.4 19.9 21.1 20.4 40.1 20.9 100 22.6 7.7 28.26.1 31.5 5.6

In some embodiments, the Compound 1 1-Hydroxy-2-napthoate (Form D)exhibits an XRPD that is substantially similar to FIG. 86.

Cyclamate Salt

In some embodiments, the present disclosure provides a cyclamate salt ofCompound 1 (“Compound 1 Cyclamate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Cyclamate.

In one embodiment, the present disclosure provides Compound 1 Cyclamate(Form A). In some embodiments, the Compound 1 Cyclamate (Form A)exhibits an XRPD comprising one or more peaks at about 6.6, 7.2, 18.5,19.5, and 21.6 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Cyclamate (Form A)further comprises one or more peaks at about 14.3, 14.8, 17.2, 17.6, and18.2 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Cyclamate (Form A) exhibits an XRPDcomprising peaks shown in Table 42 below:

TABLE 42 XRPD Table of Compound 1 Cyclamate (Form A) 2-Theta Intensity %6.6 100 7.2 42.7 8.6 9.3 14.3 19.8 14.8 18.7 17.2 11.3 17.6 12.9 18.224.9 18.5 28.8 19.5 27 20.9 6.1 21.6 35.6 26.1 5

In some embodiments, the Compound 1 Cyclamate (Form A) exhibits an XRPDthat is substantially similar to FIG. 87.

In some embodiments, the Compound 1 Cyclamate (Form A) exhibits a DSCthermogram comprising a endotherm at about 60.1° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 Cyclamate (Form A) exhibits aDSC thermogram comprising a endotherm at about 168.5° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 Cyclamate (Form A) exhibitsa DSC thermogram that is substantially similar to FIG. 88.

In some embodiments, the Compound 1 Cyclamate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 88. In otherembodiments, the TGA thermogram of the Compound 1 Cyclamate (Form A)exhibits a weight loss of 0.0 to 5.1% in the temperature range of 25 to180° C.

In some embodiments, the Compound 1 Cyclamate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 89. In otherembodiments, the Compound 1 Cyclamate (Form A) exhibits a gravimetricmoisture sorption of about 7.3% (by weight) at 80% Relative Humidity.

Ethane-1, 2-disulfonate Salt

In some embodiments, the present disclosure provides an ethane-1,2-disulfonate salt of Compound 1 (“Compound 1 Ethane-1,2-disulfonate”).In some embodiments, the present disclosure provides a crystalline formof Compound 1 Ethane-1,2-disulfonate.

In one embodiment, the present disclosure provides Compound 1Ethane-1,2-disulfonate (Form A). In some embodiments, the Compound 1Ethane-1,2-disulfonate (Form A) exhibits an XRPD comprising one or morepeaks at about 16.2, 16.5, 17.5, 20.7, and 21.3 degrees two-theta withthe margin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2;about ±0.1; about ±0.05; or less. In another embodiment, the XRPD of theCompound 1 Ethane-1,2-disulfonate (Form A) further comprises one or morepeaks at about 3.7, 5.5, 13.8, 14.7, and 26.0 degrees two-theta with themargin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Ethane-1,2-disulfonate (Form A)exhibits an XRPD comprising peaks shown in Table 43 below:

TABLE 43 XRPD Table of Compound 1 Ethane-1,2-disulfonate (Form A)2-Theta Intensity % 3.7 55.6 5.5 38.8 11.0 16.4 11.4 11 13.8 50.4 14.738 15.8 10.3 16.2 58 16.5 93.5 17.5 100 18.2 6.8 19.3 27.4 19.6 34.620.7 90.4 21.3 62.5 22.0 13.3 23.7 21.2 26.0 40.4 27.2 23.7 34.2 5.938.5 5.8

In some embodiments, the Compound 1 Ethane-1,2-disulfonate (Form A)exhibits an XRPD that is substantially similar to FIG. 90.

In some embodiments, the Compound 1 Ethane-1,2-disulfonate (Form A)exhibits a DSC thermogram comprising a endotherm at about 59.0° C. withthe error of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0;about ±0.5; or less. In some embodiments, the Compound 1Ethane-1,2-disulfonate (Form A) exhibits a DSC thermogram comprising aendotherm at about 154.8° C. with the error of margin of about ±2.5;about ±2.0; about ±1.5; about ±1.0; about ±0.5; or less. In someembodiments, the Compound 1 Ethane-1, 2-disulfonate (Form A) exhibits aDSC thermogram that is substantially similar to FIG. 91.

In some embodiments, the Compound 1 Ethane-1,2-disulfonate (Form A)exhibits a TGA thermogram that is substantially similar to FIG. 91. Inother embodiments, the TGA thermogram of the Compound 1Ethane-1,2-disulfonate (Form A) exhibits a weight loss of 0.0 to 0.7% inthe temperature range of 25 to 120° C.

In some embodiments, the Compound 1 Ethane-1,2-disulfonate (Form A)exhibits a DVS isotherm plot that is substantially similar to FIG. 92.In other embodiments, the Compound 1 Ethane-1,2-disulfonate (Form A)exhibits a gravimetric moisture sorption of about 12.9% (by weight) at80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1Ethane-1,2-disulfonate (Form B). In some embodiments, the Compound 1Ethane-1,2-disulfonate (Form B) exhibits an XRPD comprising one or morepeaks at about 5.5, 16.4, 17.4, 17.6, and 20.7 degrees two-theta withthe margin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2;about ±0.1; about ±0.05; or less. In another embodiment, the XRPD of theCompound 1 Ethane-1,2-disulfonate (Form B) further comprises one or morepeaks at about 10.9, 13.7, 14.6, 21.2, and 22.1 degrees two-theta withthe margin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2;about ±0.1; about ±0.05; or less

In some embodiments, the Compound 1 Ethane-1,2-disulfonate (Form B)exhibits an XRPD comprising peaks shown in Table 44 below:

TABLE 44 XRPD Table of Compound 1 Ethane-1,2-disulfonate (Form B)2-Theta Intensity % 5.5 33.4 10.9 15.5 11.4 11.1 13.7 22.1 14.6 25.315.0 7.4 15.2 6.3 15.7 8.1 16.0 7.5 16.4 100 17.4 36.4 17.6 29.9 19.610.2 20.7 42.5 21.0 6.1 21.2 16.9 22.1 16.8 24.7 5.8 25.9 14.7 26.2 5.427.1 5.3 27.4 5.4 27.9 5.2

In some embodiments, the Compound 1 Ethane-1,2-disulfonate (Form B)exhibits an XRPD that is substantially similar to FIG. 93.

Dichloroacetate Salt

In some embodiments, the present disclosure provides a dichloroacetatesalt of Compound 1 (“Compound 1 Dichloroacetate”). In some embodiments,the present disclosure provides a crystalline form of Compound 1Dichloroacetate.

In one embodiment, the present disclosure provides Compound 1Dichloroacetate (Form A). In some embodiments, the Compound 1Dichloroacetate (Form A) exhibits an XRPD comprising one or more peaksat about 3.4, 3.6, 16.2, 17.1 and 19.5 degrees two-theta with the marginof error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less. In another embodiment, the XRPD of the Compound 1Dichloroacetate (Form A) further comprises one or more peaks at about8.1, 11.4, 12.8, 16.7 and 20.0 degrees two-theta with the margin oferror of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less.

In some embodiments, the Compound 1 Dichloroacetate (Form A) exhibits anXRPD comprising peaks shown in Table 45 below:

TABLE 45 XRPD Table of Compound 1 Dichloroacetate (Form A) 2-ThetaIntensity % 3.4 100 3.6 49.1 8.1 37.7 11.0 9.6 11.4 11.6 12.8 10.8 14.77.7 16.2 42.9 16.7 9.8 17.1 58.4 17.5 7.1 19.5 43.2 20.0 14.3 21.9 8.522.7 7.3 25.5 9.3 25.8 9.1 26.6 8.2 27.2 5.1 31.0 6.6

In some embodiments, the Compound 1 Dichloroacetate (Form A) exhibits anXRPD that is substantially similar to FIG. 94.

In some embodiments, the Compound 1 Dichloroacetate (Form A) exhibits aDSC thermogram comprising a sharp endotherm at about 117.7° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 Dichloroacetate (FormA) exhibits a DSC thermogram that is substantially similar to FIG. 95.

In some embodiments, the Compound 1 Dichloroacetate (Form A) exhibits aTGA thermogram that is substantially similar to FIG. 95. In otherembodiments, the TGA thermogram of the Compound 1 Dichloroacetate (FormA) exhibits a weight loss of 0.0 to 3.7% in the temperature range of 25to 150° C.

In some embodiments, the Compound 1 Dichloroacetate (Form A) exhibits aDVS isotherm plot that is substantially similar to FIG. 96. In otherembodiments, the Compound 1 Dichloroacetate (Form A) exhibits agravimetric moisture sorption of about 1.8% (by weight) at 80% RelativeHumidity.

Malate Salt

In some embodiments, the present disclosure provides a malate salt ofCompound 1 (“Compound 1 Malate”). In some embodiments, the presentdisclosure provides a D-malate salt of Compound 1 (“Compound 1D-Malate”). In some embodiments, the present disclosure provides anL-malate salt of Compound 1 (“Compound 1 L-malate”).

In some embodiments, the present disclosure provides a crystalline formof Compound 1 Malate. In some embodiments, the present disclosureprovides a crystalline form of Compound 1 D-Malate. In some embodiments,the present disclosure provides a crystalline form of Compound 1L-Malate.

In one embodiment, the present disclosure provides Compound 1 L-Malate(Form A). In some embodiments, the Compound 1 L-Malate (Form A) exhibitsan XRPD comprising one or more peaks at about 3.2, 12.5, 14.4, 15.7, and18.4 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 L-Malate (Form A) furthercomprises one or more peaks at about 3.6, 6.1, 13.2, 18.9, and 21.1degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 L-Malate (Form A) exhibits an XRPDcomprising peaks shown in Table 46 below:

TABLE 46 XRPD Table of Compound 1 L-Malate (Form A) 2-Theta Intensity %3.2 93.3 3.6 45.4 6.1 42.2 8.4 9.8 10.4 5.9 10.6 6.2 11.1 14.2 12.2 19.512.5 68.8 13.2 47.8 14.1 7.2 14.4 53.1 15.5 16.6 15.7 63.1 16.9 12.317.1 27.8 17.8 7.6 18.0 9.5 18.4 100 18.9 43.6 19.2 11.5 20.7 16.7 21.132.6 21.2 17.9 22.6 7.7 23.1 6.3 23.4 20.3 23.9 8.8 24.5 8.9 24.9 6 26.08.5 26.4 13.8 26.8 6.9 27.4 5.5 28.5 3.5 28.9 4.6 29.2 3 29.9 4.5 32.33.9 32.6 6.3 33.0 2.4

In some embodiments, the Compound 1 L-Malate (Form A) exhibits an XRPDthat is substantially similar to FIG. 97.

In some embodiments, the Compound 1 L-Malate (Form A) exhibits a DSCthermogram comprising a sharp endotherm at about 120.9° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 L-Malate (Form A)exhibits a DSC thermogram comprising a sharp endotherm at about 142.3°C. with the error of margin of about ±2.5; about ±2.0; about ±1.5; about±1.0; about ±0.5; or less. In some embodiments, the Compound 1 L-Malate(Form A) exhibits a DSC thermogram that is substantially similar to FIG.98.

In some embodiments, the Compound 1 L-Malate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 98. In otherembodiments, the TGA thermogram of the Compound 1 L-Malate (Form A)exhibits a weight loss of 0.0 to 0.7% in the temperature range of 25 to105° C.

In some embodiments, the Compound 1 L-Malate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 99. In otherembodiments, the Compound 1 L-Malate (Form A) exhibits a gravimetricmoisture sorption of about 2.0% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 L-Malate(Form B). In some embodiments, the Compound 1 L-Malate (Form B) exhibitsan XRPD comprising one or more peaks at about 5.6, 13.4, 17.3, 20.8 and23.2 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 L-Malate (Form B) furthercomprises one or more peaks at about 3.7, 11.2, 14.4, 14.9 and 17.8degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 L-Malate (Form B) exhibits an XRPDcomprising peaks shown in Table 47 below:

TABLE 47 XRPD Table of Compound 1 L-Malate (Form B) 2-Theta Intensity %3.7 57.5 5.6 100 6.0 23.7 8.3 12.1 9.2 19.4 11.2 56.7 11.9 14.1 13.463.7 14.4 44.5 14.9 53.1 16.0 39.4 16.6 34 17.3 83.5 17.8 62.3 18.6 14.319.2 28.2 20.0 13.7 20.8 77.2 21.3 44.5 23.2 69 25.7 10.6 26.1 29.5

In some embodiments, the Compound 1 L-Malate (Form B) exhibits an XRPDthat is substantially similar to FIG. 100.

In some embodiments, the Compound 1 L-Malate (Form B) exhibits a DSCthermogram comprising an endotherm at about 108.7° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 L-Malate (Form B) exhibits aDSC thermogram comprising a sharp endotherm at about 143.3° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 L-Malate (Form B)exhibits a DSC thermogram that is substantially similar to FIG. 101.

In some embodiments, the Compound 1 L-Malate (Form B) exhibits a TGAthermogram that is substantially similar to FIG. 101. In otherembodiments, the TGA thermogram of the Compound 1 L-Malate (Form B)exhibits a weight loss of 0.0 to 1.2% in the temperature range of 25 to120° C.

In some embodiments, the Compound 1 L-Malate (Form B) exhibits a DVSisotherm plot that is substantially similar to FIG. 102. In otherembodiments, the Compound 1 L-Malate (Form B) exhibits a gravimetricmoisture sorption of about 3.5% (by weight) at 80% Relative Humidity.

Hydrochloride Salt

In some embodiments, the present disclosure provides a hydrochloridesalt of Compound 1 (“Compound 1 Hydrochloride”). In some embodiments,the present disclosure provides a crystalline form of Compound 1Hydrochloride.

In one embodiment, the present disclosure provides Compound 1Hydrochloride (Form A). In some embodiments, the Compound 1Hydrochloride (Form A) exhibits an XRPD comprising one or more peaks atabout 3.6, 5.2, 14.2, 17.4 and 17.7 degrees two-theta with the margin oferror of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less. In another embodiment, the XRPD of the Compound 1Hydrochloride (Form A) further comprises one or more peaks at about12.8, 13.4, 14.9, 18.9 and 20.4 degrees two-theta with the margin oferror of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less.

In some embodiments, the Compound 1 Hydrochloride (Form A) exhibits anXRPD comprising peaks shown in Table 48 below:

TABLE 48 XRPD Table of Compound 1 Hydrochloride (Form A) 2-ThetaIntensity % 3.6 88 5.2 100 8.7 11.2 12.1 15.1 12.8 22.6 13.4 19.5 13.810.1 14.2 57.8 14.9 29.7 15.5 9.8 16.1 11.2 17.1 13.7 17.4 79.6 17.754.6 18.3 10.6 18.9 16.4 20.4 21.1 21.2 9 22.0 15.9 22.5 6.1 28.2 8.7

In some embodiments, the Compound 1 Hydrochloride (Form A) exhibits anXRPD that is substantially similar to FIG. 103.

In some embodiments, the Compound 1 Hydrochloride (Form A) exhibits aDSC thermogram comprising an endotherm at about 225.0° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 Hydrochloride (Form A)exhibits a DSC thermogram comprising an endotherm at about 232.7° C.with the error of margin of about ±2.5; about ±2.0; about ±1.5; about±1.0; about ±0.5; or less. In some embodiments, the Compound 1Hydrochloride (Form A) exhibits a DSC thermogram that is substantiallysimilar to FIG. 104.

In some embodiments, the Compound 1 Hydrochloride (Form A) exhibits aTGA thermogram that is substantially similar to FIG. 104. In otherembodiments, the TGA thermogram of the Compound 1 Hydrochloride (Form A)exhibits a weight loss of 0.0 to 1.2% in the temperature range of 25 to150° C.

In some embodiments, the Compound 1 Hydrochloride (Form A) exhibits aDVS isotherm plot that is substantially similar to FIG. 105. In otherembodiments, the Compound 1 Hydrochloride (Form A) exhibits agravimetric moisture sorption of about 3.6% (by weight) at 80% RelativeHumidity.

In one embodiment, the present disclosure provides Compound 1Hydrochloride (Form B). In some embodiments, the Compound 1Hydrochloride (Form B) exhibits an XRPD comprising one or more peaks atabout 3.3, 7.8, 15.4, 16.6 and 23.2 degrees two-theta with the margin oferror of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less. In another embodiment, the XRPD of the Compound 1Hydrochloride (Form B) further comprises one or more peaks at about15.0, 18.8, 20.4, 23.5, and 26.5 degrees two-theta with the margin oferror of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less.

In some embodiments, the Compound 1 Hydrochloride (Form B) exhibits anXRPD comprising peaks shown in Table 49 below:

TABLE 49 XRPD Table of Compound 1 Hydrochloride (Form B) 2-ThetaIntensity % 3.3 58.7 4.9 12.3 7.8 34.4 9.8 14.2 15.0 25.8 15.4 100 16.657.7 17.6 7.3 18.8 16.1 20.4 14.6 22.7 5.8 23.2 59.2 23.5 32.2 26.5 15.426.9 8.4 28.4 5.8 31.7 9.3

In some embodiments, the Compound 1 Hydrochloride (Form B) exhibits anXRPD that is substantially similar to FIG. 106.

In some embodiments, the Compound 1 Hydrochloride (Form B) exhibits aDSC thermogram comprising an endotherm at about 87.1° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 Hydrochloride (Form B)exhibits a DSC thermogram comprising a sharp endotherm at about 207.3°C. with the error of margin of about ±2.5; about ±2.0; about ±1.5; about±1.0; about ±0.5; or less. In some embodiments, the Compound 1Hydrochloride (Form B) exhibits a DSC thermogram that is substantiallysimilar to FIG. 107.

In some embodiments, the Compound 1 Hydrochloride (Form B) exhibits aTGA thermogram that is substantially similar to FIG. 107. In otherembodiments, the TGA thermogram of the Compound 1 Hydrochloride (Form B)exhibits a weight loss of 0.0 to 0.7% in the temperature range of 25 to120° C.

In some embodiments, the Compound 1 Hydrochloride (Form B) exhibits aDVS isotherm plot that is substantially similar to FIG. 108. In otherembodiments, the Compound 1 Hydrochloride (Form B) exhibits agravimetric moisture sorption of about 2.9% (by weight) at 80% RelativeHumidity.

In one embodiment, the present disclosure provides Compound 1Hydrochloride (Form C). In some embodiments, the Compound 1Hydrochloride (Form C) exhibits an XRPD comprising one or more peaks atabout 14.6, 16.5, 18.0, 21.5, and 21.9 degrees two-theta with the marginof error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1;about ±0.05; or less. In another embodiment, the XRPD of the Compound 1Hydrochloride (Form C) further comprises one or more peaks at about 3.6,18.8, 19.9, 22.1, and 23.7 degrees two-theta with the margin of error ofabout ±0.5; about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05;or less.

In some embodiments, the Compound 1 Hydrochloride (Form C) exhibits anXRPD comprising peaks shown in Table 50 below:

TABLE 50 XRPD Table of Compound 1 Hydrochloride (Form C) 2-ThetaIntensity % 3.6 36.5 9.1 13.5 10.8 8.4 12.0 16.4 13.3 24.3 14.2 27.614.6 62.6 16.1 9.1 16.5 100 16.9 30.1 18.0 46.2 18.8 32.2 19.6 17.7 19.931.3 20.5 16.4 21.5 94.7 21.9 61.3 22.1 41.1 22.9 7.1 23.7 32 24.4 8.9

In some embodiments, the Compound 1 Hydrochloride (Form C) exhibits anXRPD that is substantially similar to FIG. 109.

In some embodiments, the Compound 1 Hydrochloride (Form C) exhibits aDSC thermogram comprising an endotherm at about 132.9° C. with the errorof margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5;or less. In some embodiments, the Compound 1 Hydrochloride (Form C)exhibits a DSC thermogram that is substantially similar to FIG. 110.

In some embodiments, the Compound 1 Hydrochloride (Form C) exhibits aTGA thermogram that is substantially similar to FIG. 110. In otherembodiments, the TGA thermogram of the Compound 1 Hydrochloride (Form C)exhibits a weight loss of 0.0 to 3.8% in the temperature range of 25 to120° C.

In some embodiments, the Compound 1 Hydrochloride (Form C) exhibits aDVS isotherm plot that is substantially similar to FIG. 111. In otherembodiments, the Compound 1 Hydrochloride (Form C) exhibits agravimetric moisture sorption of about 0.7% (by weight) at 80% RelativeHumidity.

Napsylate Salt

In some embodiments, the present disclosure provides a napsylate salt ofCompound 1 (“Compound 1 Napsylate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Napsylate.

In one embodiment, the present disclosure provides Compound 1 Napsylate(Form A). In some embodiments, the Compound 1 Napsylate (Form A)exhibits an XRPD comprising one or more peaks at about 3.4, 9.5, 16.6,17.0, and 17.5 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Napsylate (Form A)further comprises one or more peaks at about 8.3, 8.7, 19.8, 25.0, and25.5 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Napsylate (Form A) exhibits an XRPDcomprising peaks shown in Table 51 below:

TABLE 51 XRPD Table of Compound 1 Napsylate (Form A) 2-Theta Intensity %3.4 100 8.3 5.3 8.7 5.1 9.5 5.8 16.6 22 17.0 31.5 17.5 11.5 19.8 4.425.0 4.5 25.5 5.4

In some embodiments, the Compound 1 Napsylate (Form A) exhibits an XRPDthat is substantially similar to FIG. 112.

In some embodiments, the Compound 1 Napsylate (Form A) exhibits a DSCthermogram comprising an endotherm at about 100.1° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 Napsylate (Form A) exhibits aDSC thermogram comprising a sharp endotherm at about 202.3° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 Napsylate exhibits aDSC thermogram that is substantially similar to FIG. 113.

In some embodiments, the Compound 1 Napsylate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 113. In otherembodiments, the TGA thermogram of the Compound 1 Napsylate exhibits aweight loss of 0.0 to 1.7% in the temperature range of 25 to 180° C.

In some embodiments, the Compound 1 Napsylate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 114. In otherembodiments, the Compound 1 Napsylate (Form A) exhibits a gravimetricmoisture sorption of about 3.9% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 Napsylate(Form B). In some embodiments, the Compound 1 Napsylate (Form B)exhibits an XRPD comprising one or more peaks at about 9.1, 15.6, 16.1,18.2, and 19.7 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Napsylate (Form B)further comprises one or more peaks at about 8.6, 12.9, 17.1, 25.8, and26.2 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Napsylate (Form B) exhibits an XRPDcomprising peaks shown in Table 52 below:

TABLE 52 XRPD Table of Compound 1 Napsylate (Form B) 2-Theta Intensity %8.6 29.7 9.1 100 12.9 34.5 15.6 87.2 16.1 62.8 17.1 54.1 18.2 85.8 19.764.9 21.4 22.3 25.8 25.7 26.2 35.1

In some embodiments, the Compound 1 Napsylate (Form B) exhibits an XRPDthat is substantially similar to FIG. 115.

Oxalate Salt

In some embodiments, the present disclosure provides an oxalate salt ofCompound 1 (“Compound 1 Oxalate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 Oxalate.

In one embodiment, the present disclosure provides Compound 1 Oxalate(Form A). In some embodiments, the Compound 1 Oxalate (Form A) exhibitsan XRPD comprising one or more peaks at about 6.1, 18.2, 19.1, 19.8, and24.3 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Oxalate (Form A) furthercomprises one or more peaks at about 12.1, 13.9, 21.1, 21.7, and 24.7degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Oxalate (Form A) exhibits an XRPDcomprising peaks shown in Table 53 below:

TABLE 53 XRPD Table of Compound 1 Oxalate (Form A) 2-Theta Intensity %6.1 32.9 9.9 5.3 11.4 8.9 12.1 13.7 13.5 12.1 13.9 23.6 14.5 12.6 15.86.2 16.2 5.8 17.0 8.5 18.2 52.7 19.1 26.2 19.8 100 21.1 23.9 21.7 14.124.3 28.3 24.7 13.6 25.6 10.7 25.9 10.9 29.9 7.2 31.8 5.3 33.7 6 38.75.8

In some embodiments, the Compound 1 Oxalate (Form A) exhibits an XRPDthat is substantially similar to FIG. 116.

In some embodiments, the Compound 1 Oxalate (Form A) exhibits a DSCthermogram comprising an endotherm at about 163.8° C. with the error ofmargin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about ±0.5; orless. In some embodiments, the Compound 1 Oxalate (Form A) exhibits aDSC thermogram comprising a sharp endotherm at about 198.6° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 Oxalate exhibits aDSC thermogram that is substantially similar to FIG. 117.

In some embodiments, the Compound 1 Oxalate (Form A) exhibits a TGAthermogram that is substantially similar to FIG. 117. In otherembodiments, the TGA thermogram of the Compound 1 Oxalate exhibits aweight loss of 0.0 to 0.4% in the temperature range of 25 to 150° C.

In some embodiments, the Compound 1 Oxalate (Form A) exhibits a DVSisotherm plot that is substantially similar to FIG. 118. In otherembodiments, the Compound 1 Oxalate (Form A) exhibits a gravimetricmoisture sorption of about 1.4% (by weight) at 80% Relative Humidity.

In one embodiment, the present disclosure provides Compound 1 Oxalate(Form B). In some embodiments, the Compound 1 Oxalate (Form B) exhibitsan XRPD comprising one or more peaks at about 6.0, 6.3, 18.2, 18.8, and20.0 degrees two-theta with the margin of error of about ±0.5; about±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Oxalate (Form B) furthercomprises one or more peaks at about 12.1, 12.5, 17.8, 20.7, and 23.5degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Oxalate (Form B) exhibits an XRPDcomprising peaks shown in Table 54 below:

TABLE 54 XRPD Table of Compound 1 Oxalate (Form B) 2-Theta Intensity %6.0 37.1 6.3 56.6 9.7 13.9 9.9 13.2 12.1 27.1 12.5 34.1 13.4 23.2 14.022.5 14.9 22.5 16.9 21.6 17.8 30.4 18.2 47.3 18.8 100 19.8 23.4 20.042.9 20.7 28.3 22.7 16 23.5 33.6 25.5 9 29.5 10.2 29.9 7

In some embodiments, the Compound 1 Oxalate (Form B) exhibits an XRPDthat is substantially similar to FIG. 119.

P-Aminosalicylate Salt

In some embodiments, the present disclosure provides a p-aminosalicylatesalt of Compound 1 (“Compound 1 P-Aminosalicylate”). In someembodiments, the present disclosure provides a crystalline form ofCompound 1 P-Aminosalicylate.

In one embodiment, the present disclosure provides Compound 1P-Aminosalicylate (Form A). In some embodiments, the Compound 1P-Aminosalicylate (Form A) exhibits an XRPD comprising one or more peaksat about 5.4, 13.8, 15.7, 20.7, and 21.2 degrees two-theta with themargin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about±0.1; about ±0.05; or less. In another embodiment, the XRPD of theCompound 1 P-Aminosalicylate (Form A) further comprises one or morepeaks at about 12.5, 13.5, 15.3, 19.2, and 27.6 degrees two-theta withthe margin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2;about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 P-Aminosalicylate (Form A) exhibitsan XRPD comprising peaks shown in Table 55 below:

TABLE 55 XRPD Table of Compound 1 P-Aminosalicylate (Form A) 2-ThetaIntensity % 5.4 46.7 7.0 8.2 9.9 6.4 12.5 27.2 13.0 18.7 13.5 18.8 13.842.3 14.9 5.6 15.3 20.5 15.7 32.9 16.6 18.3 17.5 5.7 18.5 10.8 18.9 10.919.2 25.3 19.9 10.9 20.7 91.8 21.2 100 21.8 9.1 22.1 9 23.0 9.1 23.3 8.924.2 13.3 27.6 29.6 28.1 15.2

In some embodiments, the Compound 1 P-Aminosalicylate (Form A) exhibitsan XRPD that is substantially similar to FIG. 120.

In some embodiments, the Compound 1 P-Aminosalicylate (Form A) exhibitsa DSC thermogram comprising an endotherm at about 97.1° C. with theerror of margin of about ±2.5; about ±2.0; about ±1.5; about ±1.0; about±0.5; or less. In some embodiments, the Compound 1 P-Aminosalicylate(Form A) exhibits a DSC thermogram comprising a endotherm at about146.8° C. with the error of margin of about ±2.5; about ±2.0; about±1.5; about ±1.0; about ±0.5; or less. In some embodiments, the Compound1 P-Aminosalicylate (Form A) exhibits a DSC thermogram that issubstantially similar to FIG. 121.

In some embodiments, the Compound 1 P-Aminosalicylate (Form A) exhibitsa TGA thermogram that is substantially similar to FIG. 121. In otherembodiments, the TGA thermogram of the Compound 1 P-Aminosalicylate(Form A) exhibits a weight loss of 0.0 to 4.0% in the temperature rangeof 25 to 120° C.

In some embodiments, the Compound 1 P-Aminosalicylate (Form A) exhibitsa DVS isotherm plot that is substantially similar to FIG. 122. In otherembodiments, the Compound 1 P-Aminosalicylate (Form A) exhibits agravimetric moisture sorption of about 4.0% (by weight) at 80% RelativeHumidity.

In one embodiment, the present disclosure provides Compound 1P-Aminosalicylate (Form B). In some embodiments, the Compound 1P-Aminosalicylate (Form B) exhibits an XRPD comprising one or more peaksat about 12.3, 15.2, 17.3, 19.9, and 22.9 degrees two-theta with themargin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2; about±0.1; about ±0.05; or less. In another embodiment, the XRPD of theCompound 1 P-Aminosalicylate (Form B) further comprises one or morepeaks at about 6.3, 12.5, 14.8, 16.4, and 20.7 degrees two-theta withthe margin of error of about ±0.5; about ±0.4; about ±0.3; about ±0.2;about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 P-Aminosalicylate (Form B) exhibitsan XRPD comprising peaks shown in Table 56 below:

TABLE 56 XRPD Table of Compound 1 P-Aminosalicylate (Form B) 2-ThetaIntensity % 6.3 47.2 12.3 100 12.5 44.8 14.0 18 14.8 42.6 15.2 83.7 16.447.8 16.9 31.3 17.3 66.8 18.3 17.9 18.9 17.7 19.5 41.3 19.9 84.9 20.742.4 22.0 19.9 22.9 65.1 23.2 31.9 25.9 21.4 28.1 19.6 29.1 23

In some embodiments, the Compound 1 P-Aminosalicylate (Form B) exhibitsan XRPD that is substantially similar to FIG. 123.

Maleate Salt

In some embodiments, the present disclosure provides a maleate salt ofCompound 1 (“Compound 1 Maleate”). In some embodiments, the presentdisclosure provides a crystalline form of Compound 1 maleate.

In one embodiment, the present disclosure provides Compound 1 Maleate(Form A). In some embodiments, the Compound 1 Maleate (Form A) exhibitsan XRPD comprising one or more peaks at about 6.4, 9.5, 11.2, 13.1,15.0, and 17.6 degrees two-theta with the margin of error of about ±0.5;about ±0.4; about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less. Inanother embodiment, the XRPD of the Compound 1 Maleate (Form A) furthercomprises one or more peaks at about 11.2, 12.6, 14.0, 16.7, and 19.2degrees two-theta with the margin of error of about ±0.5; about ±0.4;about ±0.3; about ±0.2; about ±0.1; about ±0.05; or less.

In some embodiments, the Compound 1 Maleate (Form A) exhibits an XRPDcomprising peaks shown in Table 57 below:

TABLE 57 XRPD Table of Compound 1 Maleate (Form A) 2-Theta Intensity %6.4 100 8.1 24.2 9.5 74.6 11.2 54.4 11.6 24.6 12.6 31.0 13.1 57.1 14.039.7 15.0 86.5 16.7 46.4 17.6 65.1 19.2 44.4 23.6 21.0 24.2 16.3 24.815.9

In some embodiments, the Compound 1 Maleate (Form A) exhibits an XRPDthat is substantially similar to FIG. 124.

Methods of Preparing Salts of Compound 1

Salts of Compound 1 (and crystalline forms thereof) may be prepared, forexample, by mixing Compound 1 free base and an acid (such ashydrochloric acid) in a suitable solvent to provide the Compound 1 saltas a suspension in the suitable solvent. In some embodiments, theCompound 1 salts may be prepared by slow evaporation, slow cooling orantisolvent addition to the mixture of Compound 1 free base and an acid.

In some embodiments, the present disclosure provides methods of makingcrystalline forms of salts of Compound 1. In some embodiments, a salt ofCompound 1 is suspended in a suitable solvent for a time sufficient toprovide a suspension of a crystalline form of the salt of Compound 1.

In some embodiments, a salt of Compound 1 is dissolved in a suitablesolvent to provide a solution and a crystalline form of the salt ofCompound 1 is precipitated from the solution. In some furtherembodiments, the salt of Compound 1 is dissolved by heating a mixture ofa salt of Compound 1 and a suitable solvent. In some furtherembodiments, a crystalline form of the salt of Compound 1 isprecipitated from the solution by cooling the solution. In other furtherembodiments, the crystalline form of the salt of Compound 1 isprecipitated from the solution by adding an anti-solvent (i.e., asolvent that decreases the solubility of the crystalline form of thesalt of Compound 1) the solution. In still other further embodiments, acrystalline form of the salt of Compound 1 is precipitated from thesolution by evaporating a portion of the suitable solvent from thesolution. In certain further embodiments, the suitable solvent compriseswater.

In some embodiments, a salt of Compound 1 is heated to provide a meltand the melt is cooled to provide a crystalline form of the salt ofCompound 1. In some embodiments, a salt of Compound 1 is compressed at apressure and for a time sufficient (for example, 5 mPa for 5 minutes) toprovide a crystalline form of the salt of Compound 1. In someembodiments, a salt of Compound 1 is ground (for example, using a mortarand pestle or a mill) to provide a crystalline form of the salt ofCompound 1. In some further embodiments, a salt of Compound 1 is groundin the presence of a suitable solvent to provide crystalline form of thesalt of Compound 1. In some embodiments, a salt of Compound 1 issubjected to a relative humidity and temperature (for example, 75%relative humidity at 45° C.), for a time sufficient to provide acrystalline form of the salt of Compound 1.

In some embodiments, the suitable solvent comprises a non-proticsolvent. In some embodiments, the non-protic solvent comprises at leastone solvent selected from dimethylformamide (DMF), dimethylacetamide(DMAC), 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU),1,3-dimethyl-2-imidazolidinone (DMI), N-methylpyrrolidinone (NMP),formamide, N-methylacetamide, N-methylformamide, acetonitrile, dimethylsulfoxide, propionitrile, ethyl formate, methyl acetate, methyl ethylketone (MEK), hexachloroacetone, acetone, ethyl methyl ketone, ethylacetate, sulfolane, N,N-dimethylpropionamide, tetramethylurea,nitromethane, nitrobenzene, or hexamethylphosphoramide, diethoxymethane,tetrahydrofuran, toluene, 1,3-dioxane, 1,4-dioxane, furan, diethylether, tetrahydropyran, diisopropyl ether, dibutyl ether, ethyleneglycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycoldimethyl ether, diethylene glycol diethyl ether, triethylene glycoldimethyl ether, anisole, t-butyl methyl ether. In some embodiments, thenon-protic solvent is acetone. In some embodiments, the non-proticsolvent is ethyl acetate. In some embodiments, the non-protic solvent isacetonitrile.

In some embodiments, the suitable solvent comprises protic solvent. Insome embodiments, the protic solvent comprises at least one solventselected from water, methanol, ethanol, 2-nitroethanol, 2-fluoroethanol,2,2,2-trifluoroethanol, ethylene glycol, 1-propanol, 2-propanol,2-methoxyethanol, 1-butanol, 2-butanol, i-butyl alcohol, t-butylalcohol, 2-ethoxyethanol, diethylene glycol, 1-, 2-, or 3-pentanol,neo-pentyl alcohol, t-pentyl alcohol, diethylene glycol monomethylether, diethylene glycol monoethyl ether, cyclohexanol, benzyl alcohol,phenol, and glycerol. In some embodiments, the protic solvent comprisesa mixture of 2-propanol and water.

In some embodiments, the suitable solvent is a single solvent. In someembodiments, the solvent is a mixture of solvents. In some embodiments,the suitable solvent is a mixture of a protic solvent and a non-proticsolvent.

In certain embodiments, the Compound 1 salts (or crystalline forms ofthe salts) are isolated after they are prepared. The isolation of thesalts (or crystalline forms of the salts) may be accomplished usingmethods such as filtration, decantation, centrifugation or othersuitable separation technique.

In certain embodiments, the isolated salts (or crystalline forms of thesalts) are optionally washed with a liquid such as an anti-solvent,acetonitrile, methanol, ethanol, ethyl acetate, methyl ethyl ketone,acetone, tetrahydrofuran, or a combination thereof.

In certain embodiments, the salts of Compound 1 prepared by theembodiments above are substantially pure. For example, in someembodiments, the chemical purity of the salt of Compound 1 (for exampleCompound 1 Hydrochloride) may comprise at least about 99.9%, about99.8%, about 99.7%, about 99.6%, about 99.5%, about 99.4%, about 99.3%,about 99.2%, about 99.1%, about 99.0%, about 98%, about 97%, about 96%,or about 95% of the salt of Compound 1. Chemical purity may bedetermined using methods known to those skilled in the area (forexample, HPLC chromatography with a suitable solvent and columndetecting a wavelength of 210 nm). In some embodiments, the substantialpurity is determined on a weight percent basis. In some embodiments, thesubstantial purity is determined on an area under the curve basis.

In some embodiments, the salts of Compound 1 prepared by the embodimentsabove are crystalline. In certain embodiments, the crystalline salts ofCompound 1 prepared by the embodiments above are substantially pure. Forexample, in some embodiments, the polymorphic purity of the crystallinesalt of Compound 1 (for example Compound 1 Hydrochloride) may compriseat least about 99.9%, about 99.8%, about 99.7%, about 99.6%, about99.5%, about 99.4%, about 99.3%, about 99.2%, about 99.1%, about 99.0%,about 98%, about 97%, about 96%, about 95%, about 94%, about 93%, about92%, about 91%, about 90%, about 85%, about 80%, about 75%, about 70%,about 65%, about 60%, about 55% or about 50% of a single crystallineform (for example, Compound 1 Hydrochloride (Form A)). Polymorphicpurity may be determined using methods known to those skilled in the art(including, among others, X-ray powder crystallography as described inShah, B., et al., Analytical techniques for quantification ofamorphous/crystalline phases in pharmaceutical solids, J. Pharm. Sci.2006, 95(8), pages 1641-1665 which is hereby incorporated by referencein its entirety).

In some embodiments, the salts of Compound 1 prepared by the embodimentsabove are epimerically enriched at one or more positions compared to theepimeric purity of the Compound 1 free base starting material. Forexample, in some embodiments, the salt of Compound 1 may comprise atleast about 8:1, about 9:1, about 10:1, about 11:1, about 12:1, about13:1, about 14:1, about 15:1, or about 20:1 of 17-β: 17α epimer ofCompound 1. In some embodiments, the salt of Compound 1 may comprise atleast about 8:1, about 9:1, about 10:1, about 11:1, about 12:1, about13:1, about 14:1, about 15:1, or about 20:1 of 3α-hydroxy: 3β-hydroxy ofCompound 1. In other embodiments, the epimeric purity of the salts ofCompound 1 as described herein is substantially the same as the epimericpurity of the Compound 1 free base starting material.

Pharmaceutical Compositions

In one aspect, the present disclosure provides a pharmaceuticalcomposition comprising a salt of Compound 1. In some embodiments, thesalt of Compound 1 is Compound 1 Hydrobromide, Compound 1 Citrate,Compound 1 L-Malate, Compound 1 Mesylate, Compound 1 Phosphate, Compound1 L(+)-Tartrate, Compound 1 Hydrochloride, Compound 1 Tosylate, Compound1 Glucuronate, or Compound 1 Ethanesulfonate. In some embodiments, thesalt of Compound 1 is Compound 1 Hydrobromide (Form A). In someembodiments, the salt of Compound 1 is Compound 1 Hydrobromide (Form B).In some embodiments, the salt of Compound 1 is Compound 1 Hydrobromide(Form C). In some embodiments, the salt of Compound 1 is Compound 1Hydrobromide (Form D). In some embodiments, the salt of Compound 1 isCompound 1 Hydrobromide (Form E). In some embodiments, the salt ofCompound 1 is Compound 1 Citrate (Form A). In some embodiments, the saltof Compound 1 is Compound 1 Citrate (Form B). In some embodiments, thesalt of Compound 1 is Compound 1 Citrate (Form C).

The compositions may be administered by a suitable route, including, butnot limited to, orally, parenterally, rectally, topically and locally.The compositions may be in liquid, semi-liquid or solid form and may beformulated using methods known to those skilled in the art in a mannersuitable for each route of administration.

Orally administered dosage forms include, for example, solid dosageforms (such as tablets, capsules, pills, granules, and the like) andliquid dosage forms (such as oral solutions, oral suspensions, syrupsand the like).

In some embodiments, the pharmaceutical composition comprises atherapeutically effective amount of a salt of Compound 1 or solvatethereof and a pharmaceutically acceptable excipient.

Methods of Use

In one aspect, the present invention provides methods of treating adisease or condition in a subject in need thereof comprisingadministering to the subject a therapeutically effective amount of asalt of Compound 1.

In some embodiments, the disease or condition is depression. In someembodiments, the disease or condition is treatment resistant depression.In some embodiments, the disease or condition is post-partum depression.In some embodiments, the disease or condition is major depressivedisorder. In some embodiments, the disease or condition is bipolardisorder. In some embodiments, the disease or condition is epilepsy. Insome embodiments, the disease or condition is anxiety.

EXAMPLES

The present invention is further illustrated by reference to thefollowing Examples. However, it is noted that these Examples, like theembodiments described above, are illustrative and are not to beconstrued as restricting the scope of the invention in any way.

“EtOAc” means ethyl acetate. “(m)DSC” means (modulated) differentialscanning calorimetry. “ACN” means acetonitrile. “AR” means analyticallypure. “DCM” means dichloromethane. “DMF” means dimethyl formamide.“DMSO” means dimethylsulfoxide. “DI” means distilled. “DSC” meansdifferential scanning calorimetry. “DVS” means dynamic vapor sorption.“e.q.” means equivalents. “EtOH” means ethyl alcohol. “FaSSIF” meansfasted state simulated intestinal fluids. “FeSSIF” means fed statesimulated intestinal fluids. “1H-NMR” means proton nuclear magneticresonance. “IPA” means isopropanol. “IPAC” means isopropyl acetate.“IPE” means diisopropyl ether. “LC” means low crystallinity. “MEK” meansmethyl ethyl ketone. “MeOH” means methyl alcohol. “MIBK” means methylisobutyl ketone. “MTBE” means Methyl Tert-Butyl ether. “NMR” meansnuclear magnetic resonance. “PLM” means polarized light microscope. “RH”means relative humidity. “RRT” means relative retention time. “RT” meansRoom temperature. “RT(min)” means Retention time. “SGF” means simulatedgastric fluids. “TGA” means Thermal gravimetric analysis. “THF” meansTetrahydrofuran. “UPLC” means ultra performance liquid chromatography.“XRPD” means X-ray Powder Diffractometer.

In some instances, the ratio of Compound 1: acid in the Compound 1 saltsdescribed herein was determined by the ion chromatography (IC) using thefollowing method: 25 ut of 10.0 μg/mL sample or standard were injectedinto a Dionex IonPac AG18 column with a flow rate of 1.0 mL/min anddetected by a Thermo ICS-2100 Conductivity detector. ASRS-4 mmsuppressor was set at 38 mA and the column temperature was 30° C. Thechromatographic elution was 15 mM KOH with a total run time of 20minutes.

X-Ray Powder Diffraction patterns were collected on a RigakuD/Max-2200/PC or a Bruker D8 Advance powder diffractometer. The sampleswere irradiated with copper K-alpha X-rays (λ=1.54179 Å) with thegenerator operated at 40 kV/40 mA. The samples were scanned incontinuous mode from 3° to 40° with a sample rotation speed of 15 rpmand a scanning rate of 10°/min.

Single crystal x-ray analysis: The single crystal X-ray diffraction datawere obtained was using Rigaku XtaLAB Synergy-R(Cu) (Micro-Max007HF Cumode, CuKα: λ=1.54184 Å, Hypix6000HE detector) diffractometer.

The following SCXRD Instrument parameters were used:

Instrument Rigaku XtaLAB Synergy R X-Ray sources generatorMicroMax-007HF X-ray source (Cu/kα: 1.54184 Å) Detector HyPix 6000HEdetector Goniometer Four-circle Kappa Goniometer Low Temperature DevicesCryostream-700 (Oxford Cryosystems) Software package CrysAlisPro(V1.171.40.14e)

A suitable single crystal with good diffraction quality was separatedout of the block-like crystal sample and was wrapped with Paratone-N(anoil based cryoprotectant). The crystal was mounted on a mylar loop in arandom orientation and immersed in a stream of nitrogen at thetemperature specified in the Example, below. Preliminary examination anddata collection were performed on a Rigaku XtaLAB Synergy R (CuKαradiation, λ=1.54184 Å) diffractometer and analyzed with the CrysAlisPro(Rigaku, V1.171.40.14e, 2018) software package.

Structures were solved in the ShelXT (Sheldrick, G. M. Acta Cryst. 2015,A71, 3-8.) structure solution program using Intrinsic Phasing andrefined with ShelXL (Version 2017/1; Sheldrick, G. M. Acta Cryst. 2015,C71, 3-8) refinement package using full-matrix least-squares on F²contained in OLEX2 (Dolomanov, O. V., Bourhis, L. J., Gildea, R. J,Howard, J.A.K. & Puschmann, H. J. Appl. Cryst. 2009, 42, 339-341). Allnon-hydrogen atoms were refined anisotropically. The positions of thehydrogen atoms connected with the carbon atoms were calculatedgeometrically and refined using the riding model, but the hydrogen atomsconnected with nitrogen atom and oxygen atom were refined freely basedon the Difference Fourier Map.

DSC data were collected on a TA Q2000. For each sample analyzedapproximately 1 mg of the sample was placed in a hermetic aluminum pancontaining a pinhole and heated from 25° C. to 250° C. ramped at 10°C./min.

TGA data were collected on TA Q5000. For each sample analyzedapproximately 4 mg of material was placed in an open platinum pan andheated from 30° C. to 300° C. or weight %<80% at a rate of 10° C./min.

Dynamic Vapor Sorption (DVS) were collected conducted using an SMS DVSAdvantage 1 system. For each sample analyzed approximately 10 mg ofmaterial was transferred into the DVS instrument and recorded the weightchange with respect to the atmospheric humidity at 25° C. using thefollowing parameters: Equilibrium dm/dt: 0.01%/min, (for min: 10 min andmax: 180 min); drying setting were 0% RH for 120 min; RH (%) measurementstep at 10% and RH (%) measurement step scope of 0-90-0%.

¹H-NMR were collected on a Bruker 400 MHz magnet. For each sampleanalyzed, approximately 6 mg of material was dissolved in 0.6 mL ofd₆-DMSO for analysis. As is known to those skilled in the art, therelative ppm shift and integration values for ¹H-NMR resonances may varydepending on various sample factors, including, for example, watercontent in the d₆-DMSO, ion concentration in the sample, etc. Thus, the¹H-NMR values reported in the following examples should not beconsidered characteristic for the respective salt and polymorphic form.

UPLC data were collected by injecting a 0.5 μL of sample or standardinto a Waters Acquity UPLC Shield RP18 column with a flow rate of 0.8mL/min by an Agilent 1290 UPLC (detection wavelength: 210 nm). Thecolumn was equilibrated with mobile phase A which consisted of 0.1%H₃PO₄ in water. Mobile phase B was acetonitrile (ACN). Thechromatographic elution was programed as follows with an additionalminute after for re-equilibration and a total run time of 6 minutes:

Time (mm) A(%) B(%) 0 90 10 4 10 90 5 10 90

The crystalline salts described herein were characterized by polarizedlight microscopy. In some embodiments, the crystalline salts describedherein exhibit birefringence, which indicates crystallinity.

Example 1: Preparation of Hydrobromide Salt of Compound 1

Hydrobromide Salts of Compound 1 may be prepared from Compound 1 usingthe following exemplary methods.

Compound 1 HBr (Form A):

500 mg of Compound 1 (Pattern A, see XRPD in FIG. 1) was dissolved in16.0 mL of acetone at 60° C. while stirring at 500 rpm and held at 60°C. for 1.5 hrs. 1.1 e.q. hydrobromic acid in acetone (2.565 mL, 0.5mol/L) was then added into the Compound 1 solution and incubated at 60°C. for 3 hrs, then cooled to 25° C. and held at 25° C. for overnight.This suspension was centrifuged and the precipitate collected and washedwith acetone. The obtained wet product was vacuum dried at 25° C. for 72hrs resulting in 532.16 mg of powder with a yield of 72.05%.

The resulting solid is Compound 1 HBr (Form A). The ratio of Compound1:HBr in Compound 1 HBr (Form A) is 1:1.02 as determined by ionchromatography. The XPRD is shown in FIG. 2; the DSC and TGA are shownin FIG. 3; and the DVS is shown in FIG. 4.

Compound 1 HBr (Form B):

1 g of Compound 1 HBr (Form A) was suspended in 20 mL of 0.603 wateractivity solution (14.5% water in acetone, v/v) to generate a suspensionof 50 mg/mL. The suspension was stirred at 700 rpm and held at 50° C.for 26 hours. The suspension was centrifuged and the precipitatecollected. The obtained wet product was vacuum dried at 30° C. for threedays resulting in powder with yield of 70.82%. The ratio of Compound1:HBr in Compound 1 HBr (Form B) is 1:1.01 as determined by ionchromatography. The XPRD is shown in FIG. 5; the DSC and TGA are shownin FIG. 6; and the DVS is shown in FIG. 7.

Compound 1 HBr (Form C):

500 mg of Compound 1 HBr (Form A) was dissolved in 4.5 mL of DMSO togenerate a clear solution, then 31.5 mL of water (anti-solvent) wasadded to the DMSO solution. The solution was left at room temperaturefor seven days. Afterward, the precipitated material was isolated. Theobtained wet product was vacuum dried at 30° C. for three days resultingin powder with yield of 66.1%. The ratio of Compound 1:HBr in Compound 1HBr (Form C) is 1:1.09 as determined by ion chromatography. The XPRD isshown in FIG. 8; the DSC and TGA are shown in FIG. 9; and the DVS isshown in FIG. 10.

Compound 1 HBr (Form D):

Form D is observed by VT-XRPD when heating Form B to 160° C. The XRPD isshown in FIG. 11; the TGA and DSC are shown in FIG. 12.

Compound 1 HBr (Form E):

In a 20 mL vial with stir bar, Compound 1 (1.00 g, 1.0 equiv.) in EtOH(5 mL) was stirred at 60° C. for 30 mins. HBr (48% w/w in water, 0.3 mL,1.1 equiv.) was added to the mixture and stirred at 60° C. for 1 hr. Thereaction mixture was cooled to 25° C. and ethyl acetate anti-solvent (5mL) was added to the reaction mixture and stirred for 1 hr. The mixturewas kept in an ice bath for 30 mins followed by filtration and solidswere collected and dried under vacuum at 25° C. overnight to affordCompound 1 HBr (876 mg, 73.7% yield). The XRPD is shown in FIG. 13; theDSC and TGA are shown in FIG. 14.

General Procedures to Prepare Compound 1 HBr

The following general procedures were conducted to prepare Compound 1HBr.

General Procedure 1

In a 20 mL vial with stir bar, Compound 1 (1.00 g, 1.0 equiv.) insolvent (15 mL, 15 mL/g Compound 1), was stirred at 60° C. for 30 mins.HBr (48% w/w in water, 0.3 mL, 1.1 equiv.) was added to the reaction andstirred at 60° C. for 1 hr. The reaction was cooled to 25° C. andstirred for 1 hr. The mixture was kept in ice bath for 30 mins(procedure 1-2 was kept at 25° C.) followed by filtration and solidswere collected and dried under vacuum at 25° C. overnight to affordCompound 1 HBr.

General Procedure 2

In a 20 mL vial with stir bar, Compound 1 (1.00 g, 1.0 equiv.) insolvent (3.5 mL, 3.5 mL/g Compound 1), was stirred at 60° C. for 30mins. HBr (48% w/w in water, 0.3 mL, 1.1 equiv.) in acetone (3.5 mL, 3.5mL/g Compound 1) was added to the reaction and stirred at 60° C. for 1hr. The reaction was cooled to 25° C. and stirred for 1 hr. The mixturewas kept in ice bath for 30 mins followed by filtration and solids werecollected and dried under vacuum at 25° C. overnight to afford Compound1 HBr.

General Procedure 3

In a 20 mL vial with stir bar, Compound 1 (1.00 g, 1.0 equiv.) in EtOH(5 mL, 5 mL/g Compound 1), was stirred at 60° C. for 30 mins. HBr (48%w/w in water, 0.3 mL, 1.1 equiv.) was added to the mixture and stirredat 60° C. for 1 hr. The reaction mixture was cooled to 25° C., thenanti-solvent (5 mL, 5 mL/g Compound 1) was added to the reaction mixtureand stirred for 1 hr. The mixture was kept in an ice bath for 30 minsfollowed by filtration and solids were collected and dried under vacuumat 25° C. overnight to afford Compound 1 HBr.

The following table summarizes preparations of Compound 1 HBr accordingto these general procedures:

General Procedure 1-2 1-2 1 1 1 3 Solvent Acetone 2- EtOH EtOH/H₂O MeOHEtOH/ (mL/g (15X) propanol (15X) (1:1, 15X) (15X) EtOAc Compound 1)(15X) (1:1, 14X) Weight 88.1% 66.0% 50.9% 48.0% 38.0% 73.7% Yield Purity98.5% 99.2% 99.1% 98.0% 99.6% 99.0% Form by Form A Form A Form A Form AForm A + E Form E XRPD General Procedure 1 1-2 2 2 3 3 Solvent MeOH/EtOH/ EtOH/ EtOH/ EtOH/ EtOH/ (mL/g Acetone Acetone Acetone Acetone IPEEtOAc Compound 1) (1:1, 15X) (1:1, 15X) (1:2, 10.5X) (1:4, 17.5X) (1:2,10.5X) (1:1, 20X) Weight 48.2% 64.7% 77.4% 80.2% 80.3% 65.1% YieldPurity 99.8% 99.7% 99.7% 99.6% 99.7% 99.4% Form by Form E Form A Form AForm A Form A + E Form E XRPD General Procedure 3 3 3 3 3 3 SolventEtOH/ EtOH/ EtOH/ EtOH/ EtOH/ EtOH/ (mL/g IPE EtOAc IPAc MTBE MIBKToluene Compound 1) (1:4, 17.5X) (1:1, 10X) (1:1 ,10X) (1:1, 10X) (1:1,10X (1:1, 10X) Weight 86.8% 74.4% 79.2% 82.0% 77.2% 64.4% Yield Purity99.6% 99.7% 99.8% 99.8 % 99.8% 99.9% Form by Form Form E Form Form FormE Form XRPD A + E A + E A + E A + E

Chemical and Physical Stability Test

For each salt, approximately 5 mg compound was added into an 8 mL glassvial with a multi-hole aluminum foil cap, and kept at 60° C., 40° C./75%RH for 1 week. For photostability test, the compound in vial without capwas kept in photo-stability chamber and exposed to a total illuminationof 1.2 million lux-hrs, while the sample in vial covered with aluminumfoil completely was considered as the dark control. Appearance by visualobservation were recorded followed by purity assessment and XPRD datacollection on the residual solids.

The chemical and physical stability test results for Compound 1 HBr(Form A), Compound 1 HBr (Form B), Compound 1 HBr (Form C) and Compound1 free base are shown in the following table:

XRPD Final Test Material Conditions pattern purity Compound 1 60° C., 1w Pattern A 98.2 40° C./75% RH, 1 w Pattern A 98.2 1.2 million lux-hrsPattern A 97.9 Dark control Pattern A 98.3 Hydrobromide 60° C., 1 w FormA 98.0 (Form A) 40° C./75% RH, 1 w Form A 98.2 1.2 million lux-hrs FormA 98.2 Dark control Form A 97.9 Hydrobromide 60° C., 1 w Form B 98.8(Form B) 40° C./75% RH, 1 w Form B 98.9 1.2 million lux-hrs Form B 98.4Dark control Form B 97.8 Hydrobromide 60° C., 1 w Form C + B 98.1 (FormC) 40° C./75% RH, 1 w Form C + B 98.4 1.2 million lux-hrs Form C + B98.1 Dark control Form C + B 98.0

Solubility Tests in Simulated Gastric and Intestinal Fluids

For each salt, between about 4-6 mg of Compound 1 or the salt was addedinto a 2-mL vial in triplicate. Then 1 mL of bio-relevant media (SGF,FaSSIF or FeSSIF) was added into the vial. All the vials were placed onthe thermo-mixer and kept at 37° C. while shaking at 700 rpm. If thecompounds were completely dissolved in the media, then more compound wasadded until the system became a suspension, no additional material wasadded if the concentration of the compound exceeded 25 mg/mL. Aftershaking at 37° C. for 24 hrs, 300 μL of suspension from each system wereisolated for analysis. The samples were centrifuged at 12000 rpm for 5mins and the supernatant were analyzed by UPLC after dilution by ACN:H₂O(4/1, V/V) for 10 times. The final pH values of bio-relevant media weremeasured and recorded. The solubility results (mg/mL) in bio-relevantsolutions for Compound 1 HBr (Form A), Compound 1 HBr (Form B), Compound1 HBr (Form C) and Compound 1 free base are shown in the followingtable:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Final Final Final Solute tested 24 h pH 24 h pH 24 h pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Hydrobromide 2.60 1.91 1.04 4.11 0.885.01 (Form A) Hydrobromide 1.28 1.89 0.09 5.51 0.74 4.89 (Form B)Hydrobromide 1.32 1.99 0.42 4.90 0.41 5.05 (Form C)

Single Crystal X-Ray Analysis of Compound 1 HBr Form B

The block-like single crystal of Compound 1 Hydrobromide Form B used forSCXRD characterization were crystallized from MeOH/MEK (1:3, v/v)solvent mixture by slow evaporation method.

Characterization of the salt by PLM and XRPD showed it to be Compound 1HBr Form B.

Cell parameters and an orientation matrix for data collection wereretrieved and refined (least-squares refinement) by CrysAlisPro (Rigaku,V1.171.40.14e, 2018) software using the setting angles of 45416reflections in the range 3.4880°<θ<75.8360°. The data were collected toa minimum diffraction angle (θ) of 3.506° and a maximum diffractionangle (θ) of 68.243° at 120.00 K. The final completeness is 100%. Themean I/σ of the data is 91.7 and the maximum resolution that wasachieved was 0.83 Å.

SCXRD data obtained by the methods described herein is provided in thetable below.

Temperature 120.00 (10) K a    9.28522 (4) Å b   10.84366 (4) Å  c  25.21443 (11) Å α 90° β 90° γ 90° Space group P2₁2₁2₁ Crystal systemOrthorhombic Volume 2538.734 (18) Å³ Empirical formula C₂₆H₄₁BrN₂O₃·H₂O

Single Crystal X-Ray Analysis of Compound 1 HBr Form E

The block-like single crystal of Compound 1 Hydrobromide Form E used forSCXRD characterization were crystallized from MeOH/MEK (1:3, v/v)solvent mixture by slow evaporation method. Characterization of the saltby PLM and XRPD showed it to be Compound 1 HBr Form E.

Data collection at 120 K: Cell parameters and an orientation matrix fordata collection were retrieved and refined (least-squares refinement) byCrysAlisPro (Rigaku, V1.171.40.14e, 2018) software using the settingangles of 10196 reflections in the range 3.4990°<θ<75.6570°. The datawere collected to a minimum diffraction angle (θ) of 3.508° and amaximum diffraction angle (θ) of 66.553° at 120.00 (10) K. The finalcompleteness is 100%. The mean I/σ of the data is 19.3 and the maximumresolution that was achieved was 0.84 Å.

Data collection at Room Temperature: Cell parameters and an orientationmatrix for data collection were retrieved and refined (least-squaresrefinement) by CrysAlisPro (Rigaku, V1.171.40.14e, 2018) software usingthe setting angles of 17551 reflections in the range 3.4830°<θ<75.8250°.The data were collected to a minimum diffraction angle (θ) of 3.496° anda maximum diffraction angle (θ) of 66.597° at room temperature. Thefinal completeness is 99.8%. The mean I/σ of the data is 40.0 and themaximum resolution that was achieved was 0.84 Å.

SCXRD data obtained by the methods described herein is provided in thetable below.

Temperature 120.00 (10) K Room Temperature a    7.49140 (10) Å   23.3046(5) Å b   15.0483 (2) Å   15.0483 (3) Å c   23.0349 (2) Å    7.53530(10) Å α 90° 90° β 90° 90° γ 90° 90° Space group P2₁2₁2₁ P2₁2₁2₁ Crystalsystem Orthorhombic Orthorhombic Volume 2596.79 (5) Å³ 2642.59 (8) Å³Empirical formula C₂₆H₄₁BrN₂O₃ C₂₆H₄₁BrN₂O₃

Example 2: Preparation of Citrate Salt of Compound 1

Citrate Salts of Compound 1 may be prepared from Compound 1 using thefollowing exemplary methods.

Compound 1 Citrate (Form A):

200 mg of Compound 1 was dissolved in 10.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q. Citric acidin acetone (1.027 mL, 0.5 mol/L) was then added into the Compound 1solution and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for 20 hrs. The solution was evaporated by nitrogen toremove the organic solvent. The obtained wet product was vacuum dried at25° C. for 42 hrs resulting in 218.85 mg of powder with a yield of71.1%.

The resulting solid is Compound 1 Citrate (Form A). The ratio ofCompound 1: citric acid in Compound 1 Citrate (Form A) is 1:1.23 asdetermined by ion chromatography. The XPRD is shown in FIG. 15; the DSCand TGA are shown in FIG. 16; and the DVS is shown in FIG. 17.

Compound 1 Citrate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆): δ0.48-0.88 (m, 7H) 2.03-2.22 (m, 2H) 2.46-2.86 (m, 28H) 3.00-3.17 (m, 3H)3.19-3.46 (m, 5H) 4.74-5.35 (m, 2H) 7.09 (s, 1H) 7.19 (s, 1H) 7.86 (s,1H).

Compound 1 Citrate (Form B):

500 mg of Compound 1 Citrate (Form A) was dissolved in 4.0 mL of 0.901water activity solution (65% water in acetone, v/v) to generate asuspension targeting 125 mg/mL. The suspension was stirred at 300 rpmand held at 50° C. for 3 days. The suspension was centrifuged and theprecipitate collected. The wet crude product was vacuum dried at 30° C.for one day resulting in powder with yield of 56.9%. The ratio ofCompound 1: citric acid in Compound 1 Citrate (Form B) is 1:1.17 asdetermined by ion chromatography. The XPRD is shown in FIG. 18; the DSCand TGA are shown in FIG. 19; and the DVS is shown in FIG. 20. Compound1 Citrate (Form B) was analyzed by ¹H-NMR in deuterated DMSO resultingin the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆): δ 0.53-0.79(m, 7H) 0.85-1.76 (m, 24H) 1.99-2.14 (m, 3H) 2.32-2.35 (m, 1H) 2.61-2.74(m, 6H) 3.00-3.09 (m, 2H) 4.89-5.13 (m, 1H) 6.99 (s, 1H) 7.11 (s, 1H)7.74 (s, 1H).

Compound 1 Citrate (Form C):

A sample of Compound 1 Citrate Form A was stirred as a suspension inacetonitrile at 50° C. The resultant solids were isolated by filtration.

General Procedures to Prepare Compound 1 Citrate

The following general procedures were conducted to prepare Compound 1Citrate.

General Procedure A

To a 20 mL vial equipped with stir bar, Compound (1.00 g, 1.0 equiv.)and solvent or co-solvent were charged. The resulting mixture was heatedto 60° C. for 30 mins. To the mixture was added citric acid monohydrate(0.54 g, 1.1 equiv.) in solvent or co-solvent (pre-heated todissolution) at 60° C. and stirred for 1 hr. The reaction was cooled to25° C. and stirred overnight. The suspension was filtered and the wetcake was washed with acetone. The solids were collected and dried undervacuum at 25° C. overnight to afford Compound 1 Citrate.

General Procedure A-2

To a 20 mL vial equipped with stir bar, Compound 1 (1.00 g, 1.0 equiv.)and co-solvent (10 mL, 10 mL/g Compound 1) were charged. The resultingmixture was heated to 60° C. for 30 mins. To the mixture was addedcitric acid monohydrate (0.54 g, 1.1 equiv.) in co-solvent (2 mL, 2 mL/gCompound 1) (pre-heated to dissolution) at 60° C. and stirred for 1 hr.The reaction was cooled to 0° C. (no ppt.). The mixture was dried undervacuum and added co-solvent (3 mL, 3 mL/g Compound 1) at 60° C. Thereaction was cooled to 25° C. and stirred overnight. The suspension wasfiltered and the wet cake was washed with acetone. The solids werecollected and dried under vacuum at 25° C. overnight to afford Compound1 Citrate.

General Procedure B

To a 20 mL vial equipped with stir bar, Compound 1 (1.00 g, 1.0 equiv.)and EtOH (3.5 mL, 3.5 mL/g Compound 1) were charged. The resultingmixture was heated to 60° C. for 30 mins. To the mixture was addedcitric acid monohydrate (0.54 g, 1.1 equiv.) in EtOH (1.5 mL, 1.5 mL/gCompound 1) (pre-heated to dissolution) at 60° C. and stirred for 1 hr.The reaction was cooled to 25° C. and added anti-solvent (5 mL, 5 mL/gCompound 1) at 25° C. The reaction was cooled to 0° C. and then stirredfor 1 hr. The mixture was stirred at 25° C. overnight. The reaction wascooled to 0° C. and then stirred for 1 hr. The suspension was filteredand the wet cake was washed with acetone. The solids were collected anddried under vacuum at 25° C. overnight to afford Compound 1 Citrate.

General Procedure C

To a four-neck 250 mL flask equipped with a mechanical stirrer (5.5 cmpaddle; 100 rpm), thermometer, and N2 inlet, Compound 1 (5.00 g, 1.0equiv.) and EtOH/IPAc (1:1, 40 mL, 8 mL/g Compound 1) were charged. Theresulting mixture was heated to 60° C. for 30 mins. To the mixture wasadded citric acid monohydrate (2.73 g, 1.1 equiv.) in EtOH/IPAc (1:1, 10mL, 2 mL/g Compound 1) (pre-heated to dissolution) at 60° C., andstirred for 1 hr. The reaction was cooled to 25° C. and then stirred for1 hr. The reaction was cooled to 0° C. and then stirred for 30 mins. Thesuspension was filtered and the wet cake was washed with acetone. Thesolids were collected and dried under vacuum at 50° C. overnight toafford Compound 1 Citrate.

The following table summarizes preparations of Compound 1 Citrateaccording to these general procedures:

Preparation General 1 2 3 4 5 6 7 Procedure A C A A A A-2 B SolventAcetone EtOH/ 10-20% 1- EtOH EtOH/ EtOH/ (mL/g (30X) IPAc EtOH butanol(5X) Acetone EtOAc Compound 1) (1:1, 10X) in H₂O (10X) (1:1, (1:1, 10X)(20X) 12X→3X) Weight Yield 67.0% 90.0% 60.7% 75.1% 66.1% 63.8% 67.5%Purity 99.0% 99.6 % 98.2% 99.01% 99.4% 99.6 % 99.6 % Form by Form A FormA Form C Form A Form A Form A Form A XRPD Preparation General 8 9 10 1112 13 14 Procedure B B B B B B B Solvent EtOH/ EtOH/ EtOH/ EtOH/ EtOH/EtOH/ EtOH/ (mL/g IPE IPAc IPAc MTBE MIBK Toluene H₂O Compound 1) (1:1,10X) (1:1, 10X) (1:1, 10X) (1:1, 10X) (1:1, 10X) (1:1, 10X) (1:1, 10X)Weight Yield 82.2% 74.8% 76.2% 75.2% 71.5% 66.0% 47.7% Purity 99.0%99.1% 99.80%  99.0% 99.2% 99.7% 99.4% Form by Form A Form A Form A FormA Form A Form A Form A XRPD N.R. means that free base was recovered fromthe experiment.

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Citrate (Form A), Compound 1 Citrate (FormB) and Compound 1 free base are shown in the following table:

XRPD Final Test Material Conditions patterns purity Compound 1 60° C., 1w Pattern A 99.3 40° C./75% RH, 1 w Pattern A 99.1 1.2 million lux-hrsPattern A 99.2 Dark control Pattern A 99.1 Citrate 60° C., 1 w Form A99.5 (Form A) 40° C./75% RH, 1 w Form A 99.4 1.2 million lux-hrs Form A99.5 Dark control Form A 99.5 Citrate 60° C., 1 w Form B 97.7 (Form B)40° C./75% RH, 1 w Form B 98.3 1.2 million lux-hrs Form B 99.3 Darkcontrol Form B 99.1

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Citrate (Form A),Compound 1 Citrate (Form B) and Compound 1 free base are shown in thefollowing table:

SGF FaSSIF FeSSIF (original pH = 1.82) (original pH = 6.50) (original pH= 4.99) Solute tested 1 h 24 h Final pH 1 h 24 h Final pH 1 h 24 h FinalpH Compound 1 3.41 2.81 2.07 0.03 0.03 6.47 0.87 0.95 5.00 Citrate 4.234.27 3.00 0.18 0.16 4.85 2.18 0.38 4.71 (Form A) Citrate N/A 8.00 2.79N/A 0.33 5.05 N/A 0.37 5.13 (Form B)

Single Crystal X-Ray Structure of Compound 1 Citrate Form A

A block-like single crystal sample Compound 1 Citrate Form A used forSCXRD characterization was crystallized from THF solvent by slowevaporation method.

Characterization of the salt by PLM and XRPD showed it to be Compound 1Citrate Form A.

Cell parameters and an orientation matrix for data collection wereretrieved and refined (least-squares refinement) by CrysAlisPro (Rigaku,V1.171.40.14e, 2018) software using the setting angles of 64393reflections in the range 3.7580°<θ<75.8720°. The data were collected toa minimum diffraction angle (θ) of 3.785° and a maximum diffractionangle (θ) of 66.597° at 120.00 K. The final completeness is 99.3%. Themean I/σ of the data is 81.3 and the maximum resolution that wasachieved was 0.84 Å.

SCXRD data obtained by the methods described herein is provided in thetable below.

Temperature 120.00 (10) K a    8.85550 (10) Å b   12.18980 (10) Å c  16.49670 (10) Å α   73.6770 (10)° β   76.5960 (10)° γ   83.2390 (10)°Space group P1 Crystal system Triclinic Volume 1659.80 (3) Å³ Empiricalformula (C₂₆H₄₂N₂O₃)⁺·(C₆H₆O₇)⁻·H₂O

Example 3: Preparation of Mesylate Salt of Compound 1

A Mesylate Salt of Compound 1 may be prepared from Compound 1 using thefollowing exemplary methods.

Compound 1 Mesylate (Form A):

200 mg of Compound 1 was dissolved in 10.0 mL of EtOAc at 60° C. whilestirring at 500 rpm and held at 60° C. for 1 hr. 1.1 e.q.methanesulfonic acid in EtOAc (1.027 mL, 0.5 mol/L) was then added intothe Compound 1 solution and incubated at 60° C. for 3 hrs, then cooledto 25° C. and held at 25° C. for 20 hrs. This suspension was centrifugedand the precipitate collected and washed with EtOAc. The obtained wetproduct was vacuum dried at 35° C. for 22 hrs resulting in 234.52 mg ofpowder with a yield of 94.1%.

The resulting solid is Compound 1 Mesylate (Form A). The ratio ofCompound 1: methanesulfonic acid in Compound 1 Mesylate (Form A) is1:1.08 as determined by ion chromatography. The XPRD is shown in FIG.22; the DSC and TGA are shown in FIG. 23; and the DVS is shown in FIG.24.

Compound 1 Mesylate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆): δ0.54-0.81 (m, 7H) 0.84 (t, J=7.44 Hz, 1H) 1.84-2.17 (m, 3H) 2.31 (s, 3H)2.41-2.59 (m, 20H) 2.65-2.83 (m, 1H) 3.05 (s, 2H) 3.22-3.48 (m, 1H)3.23-3.51 (m, 6H) 4.96-5.52 (m, 1H) 4.96-5.52 (m, 1H) 7.62 (s, 1H)7.55-7.64 (m, 1H) 7.62-7.77 (m, 1H) 9.01 (s, 1H).

Compound 1 Mesylate (Form B):

200 mg of Compound 1 was dissolved in 10.0 mL of EtOAc at 60° C. whilestirring at 500 rpm and held at 60° C. for 1 hr. 1.1 e.q. methanesulfonic acid in EtOAc (1.027 mL, 0.5 mol/L) was then added into theCompound 1 solution and incubated at 60° C. for 3 hrs, then cooled to25° C. and held at 25° C. for 20 hrs. This suspension was centrifugedand the precipitate collected and washed with EtOAc. The obtained wetproduct was vacuumed dried at 35° C. for 22 hrs resulting in 234.52 mgpowder with a yield of 94.1%.

The resulting solid is Compound 1 Mesylate (Form B). The XPRD is shownin FIG. 25A.

Compound 1 Mesylate (Form C):

Compound 1 Mesylate (Form C) was prepared using solvent ACN solvent andmethane sulfonic acid. For liquid counter-ion, 50 mg Compound 1 wasweighed into 2 mL vials, and 743 μL solvents were added in the vialssubsequently. Then 1.1 e.g. counter-ions solutions of correspondingsolvent (257 μL, concentration: 0.5 mol/L) was added to the vial. Thevial was placed on the thermo-mixer with a stirrer bar and heated to 50°C. After keeping at 50° C. under stirring at 900 rpm for 18 hrs, thevial was then cooled to 25° C. After keeping at 25° C. for 1 hr, thesolids in suspensions were isolated by centrifugation and dried in thevacuum oven at 30° C. overnight.

The resulting solid is Compound 1 Mesylate (Form C). The XPRD is shownin FIG. 25B.

Compound 1 Mesylate (Form D):

Approximately 5 mg Compound 1 Mesylate (Form A) was added into an 8 mLglass vial with a multi-hole aluminum foil cap, and kept at 60° C., 40°C./75% RH for 1 week. Appearance by visual observation were recordedfollowed by purity assessment and XPRD data collection on the residualsolids. The resulting solid is Compound 1 Mesylate (Form D). The driedsolids were characterized by PLM and XRPD.

The XPRD is shown in FIG. 26.

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Mesylate (Form A) and Compound 1 free baseare shown in the following table:

XRPD Final Test material Conditions patterns purity Compound 1 60° C., 1w Pattern A 99.3 40° C./75% RH, 1 w Pattern A 99.1 1.2 million lux-hrsPattern A 99.2 Dark control Pattern A 99.1 Mesylate 60° C., 1 w Form A99.4 (Form A) 40° C./75% RH, 1 w Form D 99.4 (see FIG. 26) 1.2 millionlux-hrs Form A 99.3 Dark control Form A 99.4

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Mesylate (Form A) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original pH = 1.82) (original pH = 6.50) (original pH= 4.99) Solute tested 1 h 24 h Final pH 1 h 24 h Final pH 1 h 24 h FinalpH Compound 1 3.41 2.81 2.07 0.03 0.03 6.47 0.87 0.95 5.00Mesylate >29.38 >26.49 2.07 0.10 0.09 5.16 1.66 0.004 5.05 (Form A)

Example 4: Preparation of Phosphate Salt of Compound 1

A Phosphate Salt of Compound 1 may be prepared from Compound 1 using thefollowing exemplary method.

200 mg of Compound 1 was dissolved in 10.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q. phosphoricacid in acetone (1.027 mL, 0.5 mol/L) was then added into the Compound 1solution and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for 20 hrs. This suspension was centrifuged and theprecipitate collected and washed with acetone. The obtained wet productwas vacuum dried at 30° C. for 42 hrs resulting in 233.51 mg of powderwith a yield of 93.3%.

The resulting solid is Compound 1 Phosphate (Form A). The ratio ofCompound 1: phosphoric acid in Compound 1 Phosphate (Form A) is 1:0.9 asdetermined by ion chromatography. The XPRD is shown in FIG. 27; the DSCand TGA are shown in FIG. 28; and the DVS is shown in FIG. 29.

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Phosphate (Form A) and Compound 1 free baseare shown in the following table:

XRPD Final Test Material Conditions patterns purity Compound 1 60° C., 1w Pattern A 99.3 40° C./75% RH, 1 w Pattern A 99.1 1.2 million lux-hrsPattern A 99.2 Dark control Pattern A 99.1 Phosphate 60° C., 1 w Form A99.2 (Form A) 40° C./75% RH, 1 w Form A 99.2 1.2 million lux-hrs Form A98.9 Dark control Form A 99.2

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Phosphate (Form A) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original pH = 1.82) (original pH = 6.50) (original pH= 4.99) Solute tested 1 h 24 h Final pH 1 h 24 h Final pH 1 h 24 h FinalpH Compound 1 3.41 2.81 2.07 0.03 0.03 6.47 0.87 0.95 5.00 Phosphate18.94 14.26 2.47 0.72 0.70 4.28 1.62 0.004 4.94 (Form A)

Example 5: Preparation of L(+)-Tartrate Salt of Compound 1

L(+)-Tartrate Salts of Compound 1 may be prepared from Compound 1 usingthe following exemplary methods.

Compound 1 L(+)-Tartrate (Form A):

200 mg of Compound 1 was dissolved in 10.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.L(+)-tartaric acid powder (77 mg, 0.5 mmol) was then added into theCompound 1 solution and incubated at 60° C. for 3 hrs, then cooled to25° C. and held at 25° C. for 20 hrs. The suspension was centrifuged andthe precipitate collected and washed with acetone. The obtained wetproduct was vacuum dried at 30° C. for 42 hrs resulting in 237.95 mg ofpowder with a yield of 85.9%.

The resulting solid is Compound 1 L(+)-Tartrate (Form A). The ratio ofCompound 1: tartaric acid in Compound 1 L(+)-Tartrate (Form A) is 1:1.15as determined by ion chromatography. The XPRD is shown in FIG. 30; theDSC and TGA are shown in FIG. 31; and the DVS is shown in FIG. 32.

Compound 1 L(+)-Tartrate (Form A) was analyzed by ¹H-NMR in deuteratedDMSO resulting in the following chemical shifts: ¹H NMR (400 MHz,DMSO-d₆): δ 0.49-0.84 (m, 7H) 0.90-1.75 (m, 21H) 1.94-2.21 (m, 3H)2.35-2.58 (m, 14H) 2.66-2.80 (m, 1H) 3.10 (s, 2H) 3.23-3.34 (m, 3H)4.24-4.39 (m, 2H) 4.80-5.19 (m, 2H) 6.98 (s, 1H) 7.12 (s, 1H) 7.67 (s,1H).

Compound 1 L(+)-Tartrate (Form B):

200 mg of Compound 1 was dissolved in 10.0 mL of EtOAc at 60° C. whilestirring at 500 rpm and held at 60° C. for 1 hr. 1.1 e.q. L(+)-tartaricacid powder (77 mg, 0.5 mmol) was then added into the RX-0001175solution and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for 20 hrs. The suspension was centrifuged and theprecipitate collected and washed with EtOAc. The obtained wet productwas vacuum dried at 35° C. for 22 hrs resulting in 254.08 mg of powderwith a yield of 91.7%.

The resulting solid is Compound 1 L(+)-Tartrate (Form B). The ratio ofCompound 1: tartaric acid in Compound 1 L(+)-Tartrate (Form B) is 1:1.19as determined by ion chromatography. The XPRD is shown in FIG. 33; theDSC and TGA are shown in FIG. 34; and the DVS is shown in FIG. 35.

Compound 1 L(+)-Tartrate (Form B) was analyzed by ¹H-NMR in deuteratedDMSO resulting in the following chemical shifts: ¹H NMR (400 MHz,DMSO-d₆): δ 0.50-0.82 (m, 6H) 1.91-2.22 (m, 2H) 3.03 (s, 2H) 3.24 (s,2H) 3.14-3.53 (m, 1H) 4.27 (s, 2H) 4.54-5.21 (m, 2H) 6.71-7.18 (m, 2H)7.59 (s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 L(+)-Tartrate (Form A), Compound 1L(+)-Tartrate (Form B), and Compound 1 free base are shown in thefollowing table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 99.3 40° C./75% RH, 1 w Pattern A 99.1 1.2 millionlux-hrs Pattern A 99.2 Dark control Pattern A 99.1 L(+)-Tartrate 60° C.,1 w Form A 99.3 (Form A) 40° C./75% RH, 1 w Form A 99.3 1.2 millionlux-hrs Form A 99.4 Dark control Form A 99.2 L(+)-Tartrate 60° C., 1 wForm B 99.2 (Form B) 40° C./75% RH, 1 w Form B 99.2 1.2 million lux-hrsForm B 99.3 Dark control Form B 99.2

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 L(+)-Tartrate (Form A),Compound 1 L(+)-Tartrate (Form B), and Compound 1 free base are shown inthe following table:

SGF FaSSIF FeSSIF (original pH = 1.82) (original pH = 6.50) (original pH= 4.99) Solute tested 1 h 24 h Final pH 1 h 24 h Final pH 1 h 24 h FinalpH Compound 1 3.41 2.81 2.07 0.03 0.03 6.47 0.87 0.95 5.00 L(+)- 5.765.82 2.91 0.58 0.54 4.32 1.98 1.07 4.79 Tartrate (Form A) L(+)- 6.035.42 2.77 0.61 0.56 4.35 2.11 0.98 4.79 Tartrate (Form B)

Example 6: Preparation of Fumarate of Compound 1

Fumarate Salts of Compound 1 may be prepared from Compound 1 using thefollowing exemplary method.

Compound 1 Fumarate (Form A):

200 mg of Compound 1 was dissolved in 10.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q. fumaricacid powder (60 mg, 0.51 mmol) was then added into the Compound 1solution and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for 20 hrs. A 2-fold volume of heptane was then added tothe acetone mixture which produced a suspension. This suspension wascentrifuged and the precipitate collected, then vacuum dried at 25° C.for 42 hrs resulting in 75.58 mg of powder with a yield of 29.1%.

The resulting solid is Compound 1 Fumarate (Form A). The ratio ofCompound 1: fumaric acid in Compound 1 Fumarate (Form A) is 1:1.37 asdetermined by ion chromatography. The XPRD is shown in FIG. 36 and theDSC and TGA are shown in FIG. 37.

Compound 1 Fumarate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆): δ0.45-0.80 (m, 7H) 1.97-2.13 (m, 3H) 2.47-2.58 (m, 12H) 2.63-2.78 (m, 1H)2.63-2.78 (m, 1H) 3.04 (s, 2H) 3.25 (s, 3H) 4.80-5.14 (m, 1H) 4.80-5.14(m, 1H) 6.63 (s, 3H) 6.91 (s, 1H) 7.05 (s, 1H) 7.52-7.69 (m, 1H).

Compound 1 Fumarate (Form B):

200 mg of Compound 1 was dissolved in 10.0 mL of ethyl acetate at 60° C.while stirring at 500 rpm and held at 60° C. for 1 hr. 1.1 e.g. fumaricacid powder (60 mg, 0.51 mmol) was added into the Compound 1 solution.The solution was held at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for 20 hrs. During the cooling process, the clearsolution became suspension. This suspension was subsequently centrifugedand the precipitate collected and vacuumed dried at 35° C. for 22 hrsresulting in 156.78 mg of powder with a yield of 60.4%.

The resulting solid is Compound 1 Fumarate (Form B). The ratio ofCompound 1: fumaric acid in Compound 1 Fumarate (Form B) is 1:1.55 asdetermined by ion chromatography. The XPRD is shown in FIG. 38; the DSCand TGA are shown in FIG. 39; and the DVS is FIG. 40.

¹H NMR (400 MHz, DMSO-d₆): δ 0.43-0.79 (m, 8H) 1.88-2.13 (m, 2H) 3.03(s, 2H) 3.10-3.39 (m, 4H) 4.38-5.21 (m, 3H) 6.61 (s, 2H) 6.59-6.64 (m,1H) 6.74-7.16 (m, 2H) 7.56 (s, 1H).

Compound 1 Fumarate (Form C):

50 mg Compound 1 and 1.1 e.g. counter ion of fumaric acid in solid formwere weighed into 2 mL vials individually, followed by adding 1 mLsolvent ACN into the vial. The vial was placed on the thermo-mixer witha stir bar and heated to 50° C. After keeping at 50° C. under constantstirring at 900 rpm for 18 hrs, the vial was then cooled to 25° C. Afterkeeping at 25° C. for 1 hr, the solids in suspension were isolated bycentrifugation and dried in the vacuum oven at 30° C. for 48 hrs.

The resulting solid is Compound 1 Fumarate (Form C). The dried solidswere characterized by PLM and XRPD.

The XPRD is shown in FIG. 41.

Compound 1 Fumarate (Form D):

Approximately 5 mg Compound 1 Fumarate (Form A) was added into an 8 mLglass vial with a multi-hole aluminum foil cap, and kept at 60° C., 40°C./75% RH for 1 week. Appearance by visual observation were recordedfollowed by purity assessment and XPRD data collection on the residualsolids. The resulting solid is Compound 1 Fumarate (Form D). The driedsolids were characterized by PLM and XRPD. The XPRD is shown in FIG. 42.

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Fumarate (Form A), and Compound 1 free baseare shown in the following table:

XRPD Final Start material Condition pattern purity Compound 1 60° C., 1w Pattern A 99.3 40° C./75% RH, 1 w Pattern A 99.1 1.2 million lux-hrsPattern A 99.2 Dark control Pattern A 99.1 Fumarate 60° C., 1 w Form A88.4 (Form A) 40° C./75% RH, 1 w Form D 97.9 (see FIG. 42) 1.2 millionlux-hrs Form A 97.7 Dark control Form A 97.1

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Fumarate (Form A), andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF Solute (original pH = 1.82) (original pH = 6.50)(original pH = 4.99) tested 1 h 24 h Final pH 1 h 24 h Final pH 1 h 24 hFinal pH Compound 1 3.41 2.81 2.07 0.03 0.03 6.47 0.87 0.95 5.00Fumarate 2.90 3.03 2.39 0.25 0.32 4.63 2.06 0.72 4.58 (Form A)

Example 7: Preparation of Tosylate Salt of Compound 1

A Tosylate Salt of Compound 1 may be prepared from Compound 1 using thefollowing exemplary methods.

Compound 1 Tosylate (Form A):

200 mg of Compound 1 was dissolved in 10.0 mL of ACN at 60° C. whilestirring at 500 rpm and held at 60° C. for 1 hr. 1.1 e.q.p-toluenesulfonic acid in ACN (1.027 mL, 0.5 mol/L) was then added intothe Compound 1 solution and incubated at 60° C. for 3 hrs, then cooledto 25° C. and held at 25° C. for 20 hrs. The suspension was centrifugedand the precipitate collected and washed with ACN. The obtained wetproduct was vacuum dried at 35° C. for 22 hrs resulting in 141.85 mg ofpowder with a yield of 49.2%.

The resulting solid is Compound 1 Tosylate (Form A). The ratio ofCompound 1: toluenesulfonic acid in Compound 1 Tosylate (Form A) is1:1.09 as determined by ion chromatography. The XPRD is shown in FIG.43; the DSC and TGA are shown in FIG. 44; and the DVS is shown in FIG.45.

Compound 1 Tosylate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆): δ0.50-0.79 (m, 7H) 1.98-2.15 (m, 3H) 2.28 (s, 4H) 2.49 (s, 23H) 2.60-2.76(m, 1H) 3.03 (s, 2H) 3.21-3.34 (m, 5H) 4.85-5.45 (m, 2H) 7.10 (d, J=7.78Hz, 2H) 7.45 (s, 1H) 7.46-7.73 (m, 3H) 8.99 (s, 1H).

Compound 1 Tosylate (Form B):

50 mg Compound 1 and 1.1 e.g. counter ion of para-toluenesulfonic acidin solid form were weighed into 2 mL vials individually, and then 1 mLEtOAc solvent was added into the vial. The vial was placed on thethermo-mixer with a stir bar and heated to 50° C. After keeping at 50°C. under constant stirring at 900 rpm for 18 hrs, the vial was thencooled to 25° C. After keeping at 25° C. for 1 hr, the solids insuspension were isolated by centrifugation and dried in the vacuum ovenat 30° C. overnight.

The resulting solid is Compound 1 Tosylate (Form B). The XPRD is shownin FIG. 46.

Compound 1 Tosylate (Form C):

Approximately 5 mg Compound 1 Tosylate (Form A) was added into an 8 mLglass vial with a multi-hole aluminum foil cap, and kept at 60° C., 40°C./75% RH for 1 week. Appearance by visual observation were recordedfollowed by purity assessment and XPRD data collection on the residualsolids. The resulting solid is Compound 1 Tosylate (Form C). The driedsolids were characterized by PLM and XRPD.

The resulting solid is Compound 1 Tosylate (Form C). The XPRD is shownin FIG. 47.

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Tosylate (Form A) and Compound 1 free baseare shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 99.3 40° C./75% RH, 1 w Pattern A 99.1 1.2 millionlux-hrs Pattern A 99.2 Dark control Pattern A 99.1 Tosylate 60° C., 1 wForm A 99.5 (Form A) 40° C./75% RH, 1 w Form C 99.5 (see FIG. 47) 1.2million lux-hrs Form A 99.0 Dark control Form A 99.5

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Tosylate (Form M andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original pH = 1.82) (original pH = 6.50) (original pH= 4.99) Solute tested 1 h 24 h Final pH 1 h 24 h Final pH 1 h 24 h FinalpH Compound 1 3.41 2.81 2.07 0.03 0.03 6.47 0.87 0.95 5.00 Tosylate 0.640.62 2.10 0.02 0.03 6.33 1.61 1.69 4.94 (Form A)

Example 8: Preparation of Glucuronate Salt of Compound 1

A Glucuronate Salt of Compound 1 may be prepared from Compound 1 usingthe following exemplary method.

Compound 1 Glucuronate (Form A)

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.D-glucuronic acid solid (248.62 mg) was then added into the Compound 1solution and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for overnight. This suspension was centrifuged and theprecipitate collected and washed with acetone. The obtained wet productwas vacuum dried at 25° C. for 72 hrs resulting in 739.32 mg of powderwith a yield of 98.76%.

The resulting solid is Compound 1 Glucuronate (Form A). The ratio ofCompound 1: glucuronic acid in Compound 1 Glucuronate (Form A) is 1:1.09as determined by ion chromatography. The XPRD is shown in FIG. 48; theDSC and TGA are shown in FIG. 49; and the DVS is shown in FIG. 50.

Compound 1 Glucuronate (Form A) was analyzed by ¹H-NMR in deuteratedDMSO resulting in the following chemical shifts: ¹H NMR (400 MHz,DMSO-d6) δ ppm 0.49-0.81 (m, 7H) 0.83-1.73 (m, 22H) 1.98-2.13 (m, 2H)2.68 (br t, J=8.76 Hz, 1H) 2.90-3.08 (m, 3H) 3.10-3.20 (m, 2H) 3.57 (d,J=9.76 Hz, 1H) 3.95-4.14 (m, 2H) 4.33 (d, J=7.75 Hz, 1H) 4.78-5.11 (m,4H) 6.51 (br s, 1H) 6.88 (s, 1H) 7.03 (s, 1H) 7.54 (s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Glucuronate (Form A) and Compound 1 freebase are shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, 1 w Pattern A 98.2 1.2 millionlux-hrs Pattern A 97.9 Dark control Pattern A 98.3 Glucoronate 60° C., 1w Form A 96.7 (Form A) 40° C./75% RH, 1 w Form A 98.0 1.2 millionlux-hrs Form A 97.5 Dark control Form A 97.5

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Glucuronate (Form A)and Compound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute Final Final Final tested 24 h pH 24 h pH 24 h pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Glucuronate 5.40 2.82 0.65 4.28 0.474.97 (Form A)

Compound 1 Glucuronate (Form B)

50 mg Compound 1 and 1.1 e.q. counter ion of D-Glucuronic acid in solidform were weighed into 2 mL vials individually, and then 1 mL solventEtOAc/ACN was added into the vial. The vial was placed on thethermo-mixer with a stir bar and heated to 50° C. After keeping at 50°C. under constant stirring at 900 rpm for 18 hrs, the vial was thencooled to 25° C. After keeping at 25° C. for 1 hr, the solids insuspension were isolated by centrifugation and dried in the vacuum ovenat 30° C. for 18 hrs.

The dried solids were characterized by PLM and XRPD (FIG. 51).

Example 9: Preparation of Ethanesulfonate Salt of Compound 1

An Ethanesulfonate Salt of Compound 1 may be prepared from Compound 1using the following exemplary method.

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.ethanesulfonic acid in acetone (2.565 mL, 0.5 mol/L) was then added intothe Compound 1 solution and incubated at 60° C. for 3 hrs, then cooledto 25° C. and held at 25° C. for overnight. This suspension wascentrifuged and the precipitate collected and washed with acetone. Theobtained wet product was vacuum dried at 25° C. for 72 hrs resulting in546.88 mg of powder with a yield of 84.68%.

The resulting solid is Compound 1 Ethanesulfonate (Form A). The ratio ofCompound 1: ethanesulfonic acid in Compound 1 Ethanesulfonate (Form A)is 1:1.17 as determined by ion chromatography. The XPRD is shown in FIG.52; the DSC and TGA are shown in FIG. 53; and the DVS is shown in FIG.54.

Compound 1 Ethanesulfonate (Form A) was analyzed by ¹H-NMR in deuteratedDMSO resulting in the following chemical shifts: ¹H NMR (400 MHz,DMSO-d₆) δ ppm 0.52-0.81 (m, 7H) 0.83-1.78 (m, 25H) 1.99-2.17 (m, 3H)2.39 (q, J=7.42 Hz, 2H) 2.69-2.80 (m, 1H) 3.05 (s, 2H) 3.43 (br s, 4H)5.11-5.46 (m, 2H) 7.54-7.77 (m, 2H) 9.02 (s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Ethanesulfonate (Form A) and Compound 1 freebase are shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, 1 w Pattern A 98.2 1.2 millionlux-hrs Pattern A 97.9 Dark control Pattern A 98.3 Ethanesulfonate 60°C., 1 w Form A 98.2 (Form A) 40° C./75% RH, 1 w Form A 98.0 1.2 millionlux-hrs Form A 97.7 Dark control Form A 97.4

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Ethanesulfonate (FormA) and Compound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Ethanesulfonate 5.85 1.88 0.39 4.59 0.765.02 (Form A)

Example 10: Preparation of Sulfate Salt of Compound 1

A Sulfate Salt of Compound 1 may be prepared from Compound 1 using thefollowing exemplary method.

200 mg of Compound 1 was dissolved in 10.0 mL of ACN at 60° C. whilestirring at 500 rpm and held at 60° C. for 1 hr. 1.1 e.q. sulfuric acidin ACN (1.027 mL, 0.5 mol/L) was then added into the Compound 1 solutionand incubated at 60° C. for 3 hrs, then cooled to 25° C. and held at 25°C. for 20 hrs. The suspension was centrifuged and the precipitatecollected and washed with ACN. The obtained wet product was vacuum driedat 35° C. for 22 hrs resulting in 177.38 mg of powder with a yield of70.9%.

The resulting solid is Compound 1 Sulfate (Form A). The ratio ofCompound 1: sulfuric acid in Compound 1 Sulfate (Form A) is 1:1.03 asdetermined by ion chromatography. The XPRD is shown in FIG. 55; the DSCand TGA are shown in FIG. 56; and the DVS is shown in FIG. 57.

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Sulfate (Form A) and Compound 1 free baseare shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 99.3 40° C./75% RH, 1 w Pattern A 99.1 1.2 millionlux-hrs Pattern A 99.2 Dark control Pattern A 99.1 Sulfate 60° C., 1 wForm A 96.2 (Form A) 40° C./75% RH, 1 w Form A 97.5 1.2 million lux-hrsForm A 97.1 Dark control Form A 97.6

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Sulfate (Form A) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original pH = 1.82) (original pH = 6.50) (original pH= 4.99) Solute tested 1 h 24 h Final pH 1 h 24 h Final pH 1 h 24 h FinalpH Compound 1 3.41 2.81 2.07 0.03 0.03 6.47 0.87 0.95 5.00 Sulfate 1.951.75 1.75 2.27 1.55 2.33 0.98 0.64 4.77 (Form A)

Example 11: Preparation of Ascorbate Salt of Compound 1

An Ascorbate Salt of Compound 1 may be prepared from Compound 1 usingthe following exemplary method.

Compound 1 Ascorbate (Form A):

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q. ascorbicacid powder (226 mg) was then added into the Compound 1 solution andincubated at 60° C. for 3 hrs, then cooled to 25° C. and held at 25° C.for overnight. This suspension was centrifuged and the precipitatecollected and washed with acetone. The obtained wet product was vacuumdried at 25° C. for 72 hrs resulting in 264.1 mg of powder with a yieldof 36.3%.

The resulting solid is Compound 1 Ascorbate (Form A). The ratio ofCompound 1: ascorbic acid in Compound 1 Ascorbate (Form A) is 1:0.98 asdetermined by ion chromatography. The XPRD is shown in FIG. 58; the DSCand TGA are shown in FIG. 59; and the DVS is shown in FIG. 60.

Compound 1 Ascorbate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆) δppm 0.51-0.81 (m, 7H) 0.83-1.76 (m, 22H) 1.98-2.14 (m, 4H) 2.33 (br s,1H) 2.64-2.72 (m, 1H) 3.04 (s, 2H) 3.25 (s, 3H) 3.41-3.45 (m, 3H) 3.73(br t, J=7.65 Hz, 1H) 4.71 (d, J=1.51 Hz, 1H) 4.87-5.11 (m, 3H) 6.98 (s,1H) 7.10 (s, 1H) 7.71 (s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Ascorbate (Form A) and Compound 1 free baseare shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, 1 w Pattern A 98.2 1.2 millionlux-hrs Pattern A 97.9 Dark control Pattern A 98.3 Ascorbate 60° C., 1 wForm A 95.7 (Form A) 40° C./75% RH, 1 w Form A 96.4 1.2 million lux-hrsForm A 96.8 Dark control Form A 96.8

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Ascorbate (Form A) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Ascorbate 4.34 2.56 0.48 5.06 1.86 4.58(Form A)

Compound 1 Ascorbate (Form B):

50 mg Compound 1 and 1.1 e.q. counter ion of ascorbic acid in solid formwere weighed into 2 mL vials individually, and then 1 mL ACN solvent wasadded into the vial. The vial was placed on the thermo-mixer with a stirbar and heated to 50° C. After keeping at 50° C. under constant stirringat 500 rpm for 21 hrs, the vial was then cooled to 25° C. After keepingat 25° C. for 1 hr, the solids in suspension were isolated bycentrifugation and dried in the vacuum oven at 30° C. for 18 hrs.

The obtained dried solids were characterized by PLM and XRPD (FIG. 61).

Example 12: Preparation of Napadisylate Salt of Compound 1

A Napadisylate Salt of Compound 1 may be prepared from Compound 1 usingthe following exemplary method.

Compound 1 Napadisylate (Form A)

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.naphthalene-1,5-disulfonic acid tetrahydrate in acetone (2.565 mL, 0.5mol/L) was then added into the Compound 1 solution and incubated at 60°C. for 3 hrs, then cooled to 25° C. and held at 25° C. for overnight.This suspension was centrifuged and the precipitate collected and washedwith acetone. The obtained wet product was vacuum dried at 25° C. for 72hrs resulting in 675.62 mg of light pink powder with a yield of 69.38%.

The resulting solid is Compound 1 Napadisylate (Form A). The ratio ofCompound 1: naphthalene-1, 5-disulfonic acid in Compound 1 Napadisylate(Form A) is 1:0.7 as determined by ion chromatography. The XPRD is shownin FIG. 62; the DSC and TGA are shown in FIG. 63; and the DVS is shownin FIG. 64.

Compound 1 Napadisylate (Form A) was analyzed by ¹H-NMR in deuteratedDMSO resulting in the following chemical shifts: ¹H NMR (400 MHz,DMSO-d₆) δ ppm 0.51-0.81 (m, 7H) 0.85-1.76 (m, 21H) 2.00-2.15 (m, 2H)2.34 (s, 1H) 2.64-2.78 (m, 1H) 3.05 (s, 2H) 3.25 (s, 4H) 5.16-5.38 (m,2H) 7.37-7.45 (m, 1H) 7.62 (s, 1H) 7.68 (s, 1H) 7.93 (d, J=6.88 Hz, 1H)8.86 (d, J=8.63 Hz, 1H) 9.01 (s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Napadisylate (Form A) and Compound 1 freebase are shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, 1 w Pattern A 98.2 1.2 millionlux-hrs Pattern A 97.9 Dark control Pattern A 98.3 Napadisylate 60° C.,1 w Form A 96.6 (Form A) 40° C./75% RH, 1 w Form A 97.4 1.2 millionlux-hrs Form A 98.0 Dark control Form A 97.8

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Napadisylate (Form A)and Compound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Napadisylate 0.13 1.88 0.10 5.61 1.065.59 (Form A)

Compound 1 Napadisylate (Form B)

50 mg Compound 1 and 1.1 e.q. counter ion of naphthalene-1,5-disulfonicacid tetrahydrate in solid form were weighed into 2 mL vialsindividually, and then 1 mL solvent IPA/water (95/5, V/V) was added intothe vial. The vial was placed on the thermo-mixer with a stir bar andheated to 50° C. After keeping at 50° C. under constant stirring at 500rpm for 21 hrs, the vial was then cooled to 25° C. After keeping at 25°C. for 1 hr, the solids in suspension were isolated by centrifugationand dried in the vacuum oven at 30° C. for 18 hrs.

The dried solids were characterized by PLM and XRPD (FIG. 65).

Example 13: Preparation of Malonate Salt of Compound 1

A Malonate Salt of Compound 1 may be prepared from Compound 1 using thefollowing exemplary method.

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q. malonicacid in acetone (2.565 mL, 0.5 mol/L) was then added into the Compound 1solution and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for overnight. This suspension was centrifuged and theprecipitate collected and washed with acetone. The obtained wet productwas vacuum dried at 25° C. for 72 hrs.

The resulting solid is Compound 1 Malonate (Form A). The ratio ofCompound 1: malonic acid in Compound 1 Malonate (Form A) is 1:1.28 asdetermined by ion chromatography. The XPRD is shown in FIG. 66; and theDSC and TGA are shown in FIG. 67.

Compound 1 Malonate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆) δppm 0.50-0.79 (m, 7H) 0.84-1.75 (m, 20H) 1.91 (s, 1H) 2.00-2.12 (m, 2H)2.65-2.73 (m, 1H) 3.04 (s, 2H) 3.13 (s, 3H) 4.92-5.15 (m, 2H) 7.03-7.20(m, 2H) 7.91 (s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Malonate (Form A) and Compound 1 free baseare shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, Pattern A 98.2 1 w 1.2 millionlux- Pattern A 97.9 hrs Dark control Pattern A 98.3 Malonate (Form 60°C., 1 w Form A 97.0 A) 40° C./75% RH, Form A 98.5 1 w 1.2 million lux-Form A 98.2 hrs Dark control Form A 99.0

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Malonate (Form A) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Malonate 4.99 2.26 0.80 4.30 2.42 4.96(Form A)

Example 14: Preparation of Besylate Salt of Compound 1

A Besylate Salt of Compound 1 may be prepared from Compound 1 using thefollowing exemplary method.

Compound 1 Besylate (Form A)

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.benzenesulfonic acid in acetone (2.565 mL, 0.5 mol/L) was then addedinto the Compound 1 solution and incubated at 60° C. for 3 hrs, thencooled to 25° C. and held at 25° C. for overnight. This suspension wascentrifuged and the precipitate collected and washed with acetone. Theobtained wet product was vacuum dried at 25° C. for 72 hrs resulting in654.68 mg of powder with a yield of 92.56%.

The resulting solid is Compound 1 Besylate (Form A). The ratio ofCompound 1: benzenesulfonic acid in Compound 1 Besylate (Form A) is1:0.94 as determined by ion chromatography. The XPRD is shown in FIG.68; the DSC and TGA are shown in FIG. 69; and the DVS is shown in FIG.70.

Compound 1 Besylate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆) δppm 0.53-0.80 (m, 7H) 0.83-1.78 (m, 21H) 1.99-2.15 (m, 3H) 2.29-2.36 (m,1H) 2.56 (br s, 1H) 2.66-2.77 (m, 1H) 3.05 (s, 2H) 3.25 (s, 4H) 4.03 (brs, 1H) 5.15-5.39 (m, 2H) 7.27-7.36 (m, 3H) 7.55-7.70 (m, 4H) 8.97 (s,1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Besylate (Form A) and Compound 1 free baseare shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, Pattern A 98.2 1 w 1.2 millionlux- Pattern A 97.9 hrs Dark control Pattern A 98.3 Besylate (Form 60°C., 1 w Form A 98.3 A) 40° C./75% RH, Form A 98.3 1 w 1.2 million lux-Form A 98.7 hrs Dark control Form A 98.4

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Besylate (Form A) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Besylate (Form A) 0.85 1.84 0.28 4.780.78 5.04

Compound 1 Besylate (Form B)

50 mg Compound 1 and 1.1 e.g. counter ion of benzenesulfonic acid insolid form were weighed into 2 mL vials individually, and then 1 mL ACNsolvent was added into the vial. The vial was placed on the thermo-mixerwith a stir bar and heated to 50° C. After keeping at 50° C. underconstant stirring at 500 rpm for 21 hrs, the vial was then cooled to 25°C. After keeping at 25° C. for 1 hr, the solids in suspension wereisolated by centrifugation and dried in the vacuum oven at 30° C. for 18hrs.

The obtained dried solids were characterized by PLM and XRPD (FIG. 71).

Example 15: Preparation of Isethionate Salt of Compound 1

An Isethionate Salt of Compound 1 may be prepared from Compound 1 usingthe following exemplary method.

Compound 1 Isethionate (Form A)

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.2-hydroxyethanesulphonic acid in acetone (2.565 mL, 0.5 mol/L) was thenadded into the Compound 1 solution and incubated at 60° C. for 3 hrs,then cooled to 25° C. and held at 25° C. for overnight. This suspensionwas centrifuged and the precipitate collected and washed with acetone.The obtained wet product was vacuum dried at 25° C. for 72 hrs resultingin 493.12 mg of powder with a yield of 74.64%.

The resulting solid is Compound 1 Isethionate (Form A). The ratio ofCompound 1: 2-hydroxyethanesulphonic acid in Compound 1 Isethionate(Form A) is 1:1.09 as determined by ion chromatography. The XPRD isshown in FIG. 72; the DSC and TGA are shown in FIG. 73; and the DVS isshown in FIG. 74.

Compound 1 Isethionate (Form A) was analyzed by ¹H-NMR in deuteratedDMSO resulting in the following chemical shifts: ¹H NMR (400 MHz,DMSO-d₆) δ ppm 0.53-0.81 (m, 7H) 0.84-1.78 (m, 22H) 2.01-2.15 (m, 3H)2.34 (br s, 1H) 2.61 (t, J=6.82 Hz, 2H) 2.66-2.78 (m, 1H) 3.05 (s, 2H)3.25 (s, 3H) 3.63 (t, J=6.75 Hz, 2H) 5.14-5.38 (m, 2H) 7.58-7.69 (m, 2H)8.99 (s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Isethionate (Form A) and Compound 1 freebase are shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, Pattern A 98.2 1 w 1.2 millionlux- Pattern A 97.9 hrs Dark control Pattern A 98.3 Isethionate 60° C.,1 w Form A 98.7 (Form A) 40° C./75% RH, Form A 98.5 1 w 1.2 million lux-Form A 98.9 hrs Dark control Form A 98.8

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Isethionate (Form A)and Compound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Isethionate (Form 4.45 1.93 1.12 4.050.76 4.98 A)

Compound 1 Isethionate (Form B)

50 mg Compound 1 was weighed into 2 mL vials, and 743 μL solventIPA/water (95/5, V/V) was added in the vials subsequently. Then 1.1 e.q.counter-ion of 2-hydroxyethanesulphonic acid (257 μL, concentration: 0.5mol/L) was added to the vial. The vial was placed on the thermo-mixerwith a stir bar and heated to 50° C. After keeping at 50° C. underconstant stirring at 500 rpm for 21 hrs, the vial was then cooled to 25°C. After keeping at 25° C. for 1 hr, the vial showed a clear solution.The solvent was evaporated by vacuum oven at 30° C.

The resulting solids were characterized by PLM and XRPD (FIG. 75).

Example 16: Preparation of Gentisate Salt of Compound 1

A Gentisate Salt of Compound 1 may be prepared from Compound 1 using thefollowing exemplary method.

Compound 1 Gentisate (Form A)

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q. gentisicacid in acetone (2.565 mL, 0.5 mol/L) was then added into the Compound 1solution and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for overnight. This suspension was centrifuged and theprecipitate collected and washed with acetone. The obtained wet productwas vacuum dried at 25° C. for 72 hrs resulting in 281.5 mg of powderwith a yield of 31.39%.

The resulting solid is Compound 1 Gentisate (Form A). The ratio ofCompound 1: gentisic acid in Compound 1 Gentisate (Form A) is 1:1.03 asdetermined by ion chromatography. The XPRD is shown in FIG. 76; the DSCand TGA are shown in FIG. 77; and the DVS is shown in FIG. 78.

Compound 1 Gentisate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆) δppm 0.53-0.80 (m, 7H) 0.85-1.72 (m, 20H) 2.00-2.13 (m, 5H) 2.66-2.74 (m,1H) 3.04 (s, 2H) 4.02 (br s, 1H) 4.90-5.12 (m, 2H) 6.71 (d, J=8.76 Hz,1H) 6.88 (dd, J=8.82, 3.06 Hz, 1H) 7.03 (s, 1H) 7.13-7.17 (m, 2H)7.78-7.86 (m, 1H) 7.81 (s, 1H) 9.01 (br s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Gentisate (Form A) and Compound 1 free baseare shown in the following table:

XRPD Final Starting materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, Pattern A 98.2 1 w 1.2 millionltvc- Pattern A 97.9 hrs Dark control Pattern A 98.3 Gentisate 60° C., 1w Form A 97.0 salt (Form A) 40° C./75% RH, 1 w Form A 97.6 1.2 millionlux- Form A 96.0 hrs Dark control Form A 97.6

Compound 1 Gentisate (Form B)

50 mg Compound 1 and 1.1 e.q. counter ion of gentisic acid in solid formwere weighed into 2 mL vials individually, and then 1 mL EtOAc solventwas added into the vial. The vial was placed on the thermo-mixer with astir bar and heated to 50° C. After keeping at 50° C. under constantstirring at 900 rpm for 18 hrs, the vial was then cooled to 25° C. Afterkeeping at 25° C. for 1 hr, the solids in suspension were isolated bycentrifugation and dried in the vacuum oven at 30° C. for 18 hrs.

The dried solids were characterized by PLM and XRPD (FIG. 79).

Compound 1 Gentisate (Form C)

50 mg Compound 1 and 1.1 e.q. counter ion of gentisic acid in solid formwere weighed into 2 mL vials individually, and then 1 mL IPA/water(95/5, V/V) solvent was added into the vial. The vial was placed on thethermo-mixer with a stir bar and heated to 50° C. After keeping at 50°C. under constant stirring at 900 rpm for 18 hrs, the vial was thencooled to 25° C. After keeping at 25° C. for 1 hr, the solids insuspension were isolated by centrifugation and dried in the vacuum ovenat 30° C. for 18 hrs.

The dried solids were characterized by PLM and XRPD (FIG. 80).

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Gentisate (Form A) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Gentisate (Form A) 1.16 1.93 0.15 5.231.20 5.01

Example 17: Preparation of 1-Hydroxy-2-Napthoate Salt of Compound 1

A 1-Hydroxy-2-Napthoate Salt of Compound 1 may be prepared from Compound1 using the following exemplary method.

Compound 1 1-Hydroxy-2-Napthoate (Form A)

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.1-hydroxy-2-napthoic acid in acetone (2.565 mL, 0.5 mol/L) was thenadded into the Compound 1 solution and incubated at 60° C. for 3 hrs,then cooled to 25° C. and held at 25° C. for overnight. This suspensionwas centrifuged and the precipitate collected and washed with acetone.The obtained wet product was vacuum dried at 25° C. for 72 hrs resultingin 675.36 mg of powder with a yield of 68.15%.

The resulting solid is Compound 1 1-Hydroxy-2-Napthoate (Form A). Theratio of Compound 1: 1-Hydroxy-2-Napthoic acid in Compound 11-Hydroxy-2-Napthoate (Form A) is 1:1.15 as determined by ionchromatography. The XPRD is shown in FIG. 81; the DSC and TGA are shownin FIG. 82; and the DVS is shown in FIG. 83.

Compound 1 1-Hydroxy-2-Napthoate (Form A) was analyzed by ¹H-NMR indeuterated DMSO resulting in the following chemical shifts: ¹H NMR (400MHz, DMSO-d₆) δ ppm 0.49-0.79 (m, 7H) 0.82-1.76 (m, 22H) 1.96-2.16 (m,4H) 2.63-2.76 (m, 1H) 2.95-3.11 (m, 2H) 4.98-5.22 (m, 2H) 7.19-7.32 (m,3H) 7.46-7.62 (m, 2H) 7.72-7.86 (m, 2H) 8.16-8.29 (m, 2H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 1-Hydroxy-2-Napthoate (Form A) and Compound1 free base are shown in the following table:

XRPD Final Starting materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.15 40° C./75% RH, Pattern A 98.23 1 w 1.2 millionlux- Pattern A 97.92 hrs Dark control Pattern A 98.30 1-hydroxy-2- 60°C., 1 w Form A 88.91 napthoate 40° C./75% RH, 1 w Form A 92.64 (Form A)1.2 million lux- Form A 92.64 hrs Dark control Form A 91.96

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 1-Hydroxy-2-Napthoate(Form A) and Compound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 1-hydroxy-2-napthoate 1.04 2.05 0.085.74 2.32 4.98 (Form A)

Compound 1 1-Hydroxy-2-Napthoate (Form B)

50 mg Compound 1 and 1.1 e.g. counter ion of 1-hydroxy-2-napthoic acidin solid form were weighed into 2 mL vials individually, and then 1 mLEtOAc solvent was added into the vial. The vial was placed on thethermo-mixer with a stir bar and heated to 50° C. After keeping at 50°C. under constant stirring at 900 rpm for 18 hrs, the vial was thencooled to 25° C. After keeping at 25° C. for 1 hr, the solids insuspension were isolated by centrifugation and dried in the vacuum ovenat 30° C. for 18 hrs.

The dried solids were characterized by PLM and XRPD (FIG. 84).

Compound 1 1-Hydroxy-2-Napthoate (Form C)

50 mg Compound 1 and 1.1 e.g. counter ion of 1-hydroxy-2-napthoic acidin solid form were weighed into 2 mL vials individually, and then 1 mLACN solvent was added into the vial. The vial was placed on thethermo-mixer with a stir bar and heated to 50° C. After keeping at 50°C. under constant stirring at 900 rpm for 18 hrs, the vial was thencooled to 25° C. After keeping at 25° C. for 1 hr, the solids insuspension were isolated by centrifugation and dried in the vacuum ovenat 30° C. for 18 hrs.

The dried solids were characterized by PLM and XRPD (FIG. 85).

Compound 1 1-Hydroxy-2-Napthoate (Form D)

50 mg Compound 1 and 1.1 e.g. counter ion of 1-hydroxy-2-napthoic acidin solid form were weighed into 2 mL vials individually, and then 1 mLsolvent IPA/water (95/5, V/V) was added into the vial. The vial wasplaced on the thermo-mixer with a stir bar and heated to 50° C. Afterkeeping at 50° C. under constant stirring at 900 rpm for 18 hrs, thevial was then cooled to 25° C. After keeping at 25° C. for 1 hr, thesolids in suspension were isolated by centrifugation and dried in thevacuum oven at 30° C. for 18 hrs.

The dried solids were characterized by PLM and XRPD (FIG. 86).

Example 18: Preparation of Cyclamate Salt of Compound 1

A Cyclamate Salt of Compound 1 may be prepared from Compound 1 using thefollowing exemplary method.

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q. cyclamicacid in acetone (2.565 mL, 0.5 mol/L) was then added into the Compound 1solution and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for overnight. This suspension was centrifuged and theprecipitate collected and washed with acetone. The obtained wet productwas vacuum dried at 25° C. for 72 hrs resulting in 715.81 mg of powderwith a yield of 74.48%.

The resulting solid is Compound 1 Cyclamate (Form A). The ratio ofCompound 1: cyclamic acid in Compound 1 Cyclamate (Form A) is 1:1.00 asdetermined by ion chromatography. The XPRD is shown in FIG. 87; the DSCand TGA are shown in FIG. 88; and the DVS is shown in FIG. 89.

Compound 1 Cyclamate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆) δppm 0.49-0.80 (m, 7H) 0.84-1.77 (m, 30H) 1.83-2.14 (m, 5H) 2.65-2.74 (m,1H) 2.90-3.09 (m, 3H) 3.35-3.60 (m, 2H) 4.03 (br s, 1H) 4.87-5.16 (m,2H) 6.97-7.18 (m, 2H) 7.54-7.91 (m, 3H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Cyclamate (Form A) and Compound 1 free baseare shown in the following table:

XRPD Final Starting materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, Pattern A 98.2 1 w 1.2 millionlux- Pattern A 97.9 hrs Dark control Pattern A 98.3 Cyclamate 60° C., 1w Form A 97.6 (Form A) 40° C./75% RH, 1 w Form A 97.5 1.2 million lux-Form A 97.2 hrs Dark control Form A 97.5

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Cyclamate (Form A) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Cyclamate (Form A) 1.99 2.05 0.57 4.500.83 5.00

Example 19: Preparation of Ethane-1,2-Disulfonate Salt of Compound 1

A Ethane-1,2-Disulfonate Salt of Compound 1 may be prepared fromCompound 1 using the following exemplary method.

Compound 1 Ethane-1,2-Disulfonate (Form A)

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.ethane-1,2-disulfonic acid in acetone (2.565 mL, 0.5 mol/L) was thenadded into the Compound 1 solution and incubated at 60° C. for 3 hrs,then cooled to 25° C. and held at 25° C. for overnight. This suspensionwas centrifuged and the precipitate collected and washed with acetone.The obtained wet product was vacuum dried at 25° C. for 72 hrs resultingin 704.45 mg of powder with a yield of 71.61%.

The resulting solid is Compound 1 Ethane-1,2-Disulfonate (Form A). Theratio of Compound 1: Ethane-1,2-Disulfonic acid in Compound 1Ethane-1,2-Disulfonate (Form A) is 1:2.4 as determined by ionchromatography. The XPRD is shown in FIG. 90; the DSC and TGA are shownin FIG. 91; and the DVS is shown in FIG. 92.

Compound 1 Ethane-1,2-Disulfonate (Form A) was analyzed by ¹H-NMR indeuterated DMSO resulting in the following chemical shifts: ¹H NMR (400MHz, DMSO-d₆) δ ppm 0.52-0.79 (m, 7H) 0.82-1.77 (m, 22H) 1.97-2.15 (m,2H) 2.58-2.78 (m, 4H) 3.03 (s, 2H) 3.23 (s, 4H) 5.13-5.40 (m, 2H)7.56-7.71 (m, 2H) 9.00 (s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Ethane-1,2-Disulfonate (Form A) and Compound1 free base are shown in the following table:

XRPD Final Starting materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, Pattern A 98.2 1 w 1.2 millionlux- Pattern A 97.9 hrs Dark control Pattern A 98.3 Ethane-1,2- 60° C.,1 w Form A 95.6 disulfonate salt 40° C./75% RH, 1 w Form A 96.0 (Form A)1.2 million lux- Form A 96.6 hrs Dark control Form A 96.8

Compound 1 Ethane-1,2-Disulfonate (Form B)

50 mg Compound 1 and 1.1 e.q. counter ion of ethane-1,2-disulfonic acidin solid form were weighed into 2 mL vials individually, and then 1 mLsolvent EtOAc/IPA/water (95/5, V/V) was added into the vial. The vialwas placed on the thermo-mixer with a stir bar and heated to 50° C.After keeping at 50° C. under constant stirring at 900 rpm for 18 hrs,the vial was then cooled to 25° C. After keeping at 25° C. for 1 hr, thesolids in suspension were isolated by centrifugation and dried in thevacuum oven at 30° C. for 18 hrs.

The dried solids were characterized by PLM and XRPD (FIG. 93).

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Ethane-1,2-Disulfonate(Form A) and Compound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Ethane-1,2-disulfonate 1.66 1.86 0.554.53 0.06 4.97 (Form A)

Example 20: Preparation of Dichloroacetate Salt of Compound 1

A Dichloroacetate Salt of Compound 1 may be prepared from Compound 1using the following exemplary method.

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.dichloroacetic acid in acetone (2.565 mL, 0.5 mol/L) was then added intothe Compound 1 solution and incubated at 60° C. for 3 hrs, then cooledto 25° C. and held at 25° C. for overnight. This suspension wascentrifuged and the precipitate collected and washed with acetone. Theobtained wet product was vacuum dried at 25° C. for 72 hrs resulting in559.98 mg of powder with a yield of 83.41%.

The resulting solid is Compound 1 Dichloroacetate (Form A). The ratio ofCompound 1: Dichloroacetic acid in Compound 1 Dichloroacetate (Form A)is 1:1.14 as determined by ion chromatography. The XPRD is shown in FIG.94; the DSC and TGA are shown in FIG. 95; and the DVS is shown in FIG.96.

Compound 1 Dichloroacetate (Form A) was analyzed by ¹H-NMR in deuteratedDMSO resulting in the following chemical shifts: ¹H NMR (400 MHz,DMSO-d₆) δ ppm 0.46-0.79 (m, 7H) 0.82-1.75 (m, 21H) 1.96-2.15 (m, 2H)2.62-2.75 (m, 1H) 3.02 (s, 2H) 4.98-5.27 (m, 3H) 6.30 (s, 1H) 7.31 (d,J=12.80 Hz, 2H) 8.32 (s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Dichloroacetate (Form A) and Compound 1 freebase are shown in the following table:

XRPD Final Starting materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, Pattern A 98.2 1 w 1.2 millionlux- Pattern A 97.9 hrs Dark control Pattern A 98.3 Dichloroacetate 60°C., 1 w Form A 96.3 (Form A) 40° C./75% RH, 1 w Form A 98.0 1.2 millionlux- Form A 96.4 hrs Dark control Form A 97.3

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Dichloroacetate (FormA) and Compound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Dichloroacetate 5.96 1.90 0.60 4.41 1.204.00 (Form A)

Example 21: Preparation of L-Malate Salt of Compound 1

L-Malate Salts of Compound 1 may be prepared from Compound 1 using thefollowing exemplary method.

Compound 1 L-Malate (Form A):

200 mg of Compound 1 was dissolved in 10.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q. L-malicacid in acetone (1.027 mL, 0.5 mol/L) was then added into the Compound 1solution and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for 20 hrs. The solution was evaporated by nitrogen toremove the organic solvent. The obtained wet product was vacuum dried at25° C. for 42 hrs resulting in 230.93 mg of powder with a yield of85.9%.

The resulting solid is Compound 1 L-Malate (Form A). The ratio ofCompound 1: Malic acid in Compound 1 L-Malate (Form A) is 1:1.35 asdetermined by ion chromatography. The XPRD is shown in FIG. 97; the DSCand TGA are shown in FIG. 98; and the DVS is shown in FIG. 99.

Compound 1 L-Malate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆): δ0.57-0.86 (m, 4H) 0.70-0.86 (m, 4H) 0.89-1.79 (m, 21H) 2.00-2.21 (m, 3H)2.33-2.78 (m, 13H) 3.10 (s, 2H) 3.31 (s, 3H) 4.28 (dd, J=7.32, 5.44 Hz,1H) 4.85-5.19 (m, 2H) 7.00 (s, 1H) 7.13 (s, 1H) 7.53-7.84 (m, 1H).

Compound 1 L-Malate (Form B):

10 g of Compound 1 was suspended in 350 mL of acetone at 60° C. whilestirring at 200 rpm and held at 60° C. for 0.5 hrs. 1.1 e.q. L-malicacid in acetone (50 mL, 0.5 mol/L) was then added into the Compound 1suspension and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for 72 hrs with vial openly. The suspension wascentrifuged and the precipitate was collected and vacuum dried at 30° C.for 24 hrs resulting in 4.44 g of powder with a yield of 33.86%.

The resulting solid is Compound 1 L-Malate (Form B). The ratio ofCompound 1: Malic acid in Compound 1 L-Malate (Form B) is 1:1.26 asdetermined by ion chromatography. The XPRD is shown in FIG. 100; the DSCand TGA are shown in FIG. 101; and the DVS is shown in FIG. 102.

Compound 1 L-Malate (Form B) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆) δppm 0.45-0.79 (m, 7H) 0.83-1.73 (m, 20H) 1.98-2.12 (m, 2H) 2.43 (dd,J=15.69, 7.40 Hz, 1H) 2.56-2.72 (m, 2H) 3.04 (s, 2H) 4.22 (dd, J=7.28,5.52 Hz, 1H) 4.86-5.10 (m, 2H) 6.94 (s, 1H) 7.07 (s, 1H) 7.65 (s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 L-Malate (Form A), Compound 1 L-Malate (FormB), and Compound 1 free base are shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 99.3 40° C./75% RH, Pattern A 99.1 1 w 1.2 millionlux- Pattern A 99.2 hrs Dark control Pattern A 99.1 L-Malate (Form 60°C., 1 w Form A 99.6 A) 40° C./75% RH, Form A 99.2 1 w 1.2 million lux-Form A 99.3 hrs Dark control Form A 99.3 L-Malate 60° C., 1 w Form B97.8 (Form B) 40° C./75% RH, Similar to Form 98.5 1 w A 1.2 million lux-Form B 97.6 hrs Dark control Form B 97.5

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 L-Malate (Form A),Compound 1 L-Malate (Form B), and Compound 1 free base are shown in thefollowing table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.50) pH= 4.99) Solute Final Final 24 Final tested 1 h 24 h PH 1 h 24 h pH 1 h hPH Compound 3.41 2.81 2.07 0.03 0.03 6.47 0.87 0.95 5.00 1 L-Malate 5.354.69 3.26 0.10 0.08 6.02 1.66 0.73 4.79 (Form A) L-Malate N/A 6.53 2.63N/A 1.12 3.98 N/A 1.25 4.01 (Form B)

Example 22: Preparation of Hydrochloride Salt of Compound 1

Hydrochloride Salts of Compound 1 may be prepared from Compound 1 usingthe following exemplary methods.

Compound 1 Hydrochloride (Form A):

200 mg of Compound 1 was dissolved in 10.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.hydrochloric acid in acetone (1.027 mL, 0.5 mol/L) was then added intothe Compound 1 solution and incubated at 60° C. for 3 hrs, then cooledto 25° C. and held at 25° C. for 20 hrs. This suspension was centrifugedand the precipitate collected and washed with acetone. The obtained wetproduct was vacuum dried at 25° C. for 42 hrs resulting in 168.15 mg ofpowder with a yield of 76.9%.

The resulting solid is Compound 1 Hydrochloride (Form A). The ratio ofCompound 1: hydrochloric acid in Compound 1 Hydrochloride (Form A) is1:0.94 as determined by ion chromatography. The XPRD is shown in FIG.103; the DSC and TGA are shown in FIG. 104; and the DVS is shown in FIG.105.

Compound 1 Hydrochloride (Form B):

500 mg of hydrochloride (Form A) was dissolved in 4.0 mL of ethanol at50° C. The solution was filtered and a 6.25 fold volume of heptane wasthen added dropwise to the solution which produced a suspension. Thissuspension was kept constant stirring at 500 rpm and held at 50° C. for24 hrs. The suspension was then centrifuged and the precipitatecollected, vacuum dried at 30° C. for 24 hrs resulting in 365 mg ofpowder with a yield of 73.0%.

The resulting solid is Compound 1 Hydrochloride (Form B). The ratio ofCompound 1: hydrochloric acid in Compound 1 Hydrochloride (Form B) is1:0.96 as determined by ion chromatography. The XPRD is shown in FIG.106; the DSC and TGA are shown in FIG. 107; and the DVS is shown in FIG.108.

Compound 1 Hydrochloride (Form C):

300 mg of hydrochloride salt (Form A) was suspended in 6.0 mL of 0.901water activity solution at 50° C. under stirring at 700 rpm whichproduced a clear solution. Then 200 mg of the hydrochloride salt wasadded which produced a suspension. The suspension remained underconstant stirring at 700 rpm and held at 50° C. for 1 week. Then thesuspension was centrifuged and the precipitate collected, vacuum driedat 30° C. for 24 hrs resulting in 400 mg of powder with a yield of80.0%.

The resulting solid is Compound 1 Hydrochloride (Form C). The ratio ofCompound 1: Hydrochloric acid in Compound 1 Hydrochloride (Form C) is1:0.97 as determined by ion chromatography. The XPRD is shown in FIG.109; the DSC and TGA are shown in FIG. 110; and the DVS is shown in FIG.111.

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Hydrochloride (Form A), Compound 1Hydrochloride (Form B), Compound 1 Hydrochloride (Form C) and Compound 1free base are shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 99.3 40° C./75% RH, Pattern A 99.1 1 w 1.2 millionlux- Pattern A 99.2 hrs Dark control Pattern A 99.1 Hydrochloride 60°C., 1 w Form A 99.5 (Form A) 40° C./75% RH, Form A 99.4 1 w 1.2 millionlux- Form A 99.5 hrs Dark control Form A 99.5 Hydrochloride 60° C., 1 wForm B 100.0 (Form B) 40° C./75% RH, Similar to 100.0 1 w Form C 1.2million lux- Form B 98.2 hrs Dark control Form B 98.59 Hydrochloride 60°C., 1 w Form C 98.6 (Form C) 40° C./75% RH, Form C 100.0 1 w 1.2 millionlux- Form C 100.0 hrs Dark control Form C 99.2

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Hydrochloride (Form A),Compound 1 Hydrochloride (Form B), Compound 1 Hydrochloride (Form C) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.50) pH= 4.99) Solute 1 24 Final Final Final tested h h pH 1 h 24 h pH 1 h 24 hpH Compound 3.41 2.81 2.07 0.03 0.03 6.47 0.87 0.95 5.00 1 Hydro- 6.286.28 2.05 0.86 0.84 4.05 1.17 0.67 4.93 chloride (Form A) Hydro- N/A3.00 1.73 N/A 1.70 3.76 N/A 1.32 3.94 chloride (Form B) Hydro- N/A 1.581.69 N/A 0.95 4.03 N/A 1.12 3.99 chloride (Form C)

Example 22: Preparation of Napsylate Salt of Compound 1

A Napsylate Salt of Compound 1 may be prepared from Compound 1 using thefollowing exemplary method.

Compound 1 Napsylate (Form A):

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.q.naphthalene-2-sulfonic acid hydrate in acetone (2.565 mL, 0.5 mol/L) wasthen added into the Compound 1 solution and incubated at 60° C. for 3hrs, then cooled to 25° C. and held at 25° C. for overnight. Thissuspension was centrifuged and the precipitate collected and washed withacetone. The obtained wet product was vacuum dried at 25° C. for 72 hrsresulting in 690.41 mg of powder with a yield of 89.17%.

The resulting solid is Compound 1 Napsylate (Form A). The ratio ofCompound 1: naphthalene-2-sulfonic acid in Compound 1 Napsylate (Form A)is 1:1.04 as determined by ion chromatography. The XPRD is shown in FIG.112; the DSC and TGA are shown in FIG. 113; and the DVS is shown in FIG.114.

Compound 1 Napsylate (Form A) was analyzed by ¹H-NMR in deuterated DMSOresulting in the following chemical shifts: ¹H NMR (400 MHz, DMSO-d₆) δppm 0.51-0.80 (m, 8H) 0.82-1.77 (m, 25H) 2.33 (br d, J=1.75 Hz, 2H)2.54-2.78 (m, 3H) 3.05 (s, 3H) 3.20-3.30 (m, 6H) 4.04 (br s, 1H)5.15-5.36 (m, 2H) 7.49-7.73 (m, 5H) 7.83-8.01 (m, 3H) 8.14 (s, 1H) 8.94(s, 1H).

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Napsylate (Form A) and Compound 1 free baseare shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, Pattern A 98.2 1 w 1.2 millionlux- Pattern A 97.9 hrs Dark control Pattern A 98.3 Napsylate (Form 60°C., 1 w Form A 99.1 A) 40° C./75% RH, Form A 99.1 1 w 1.2 million lux-Form A 99.0 hrs Dark control Form A 99.1

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Napsylate (Form A) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Napsylate (Form 0.40 1.86 0.06 5.42 1.005.04 A)

Compound 1 Napsylate (Form B):

50 mg Compound 1 and 1.1 e.q. counter ion of naphthalene-2-sulfonic acidhydrate in solid form were weighed into 2 mL vials individually, andthen 1 mL solvent EtOAc/ACN was added into the vial. The vial was placedon the thermo-mixer with a stir bar and heated to 50° C. After keepingat 50° C. under constant stirring at 500 rpm for 21 hrs, the vial wasthen cooled to 25° C. After keeping at 25° C. for 1 hr, the solids insuspension were isolated by centrifugation and dried in the vacuum ovenat 30° C. for 18 hrs.

The obtained dried solids were characterized by PLM and XRPD (FIG. 115).

Example 23: Preparation of Oxalate Salt of Compound 1

An Oxalate Salt of Compound 1 may be prepared from Compound 1 using thefollowing exemplary method.

Compound 1 Oxalate (Form A)

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 e.g. oxalic acidin acetone (2.565 mL, 0.5 mol/L) was then added into the Compound 1solution and incubated at 60° C. for 3 hrs, then cooled to 25° C. andheld at 25° C. for overnight. This suspension was centrifuged and theprecipitate collected and washed with acetone. The obtained wet productwas vacuum dried at 25° C. for 72 hrs resulting in 595.76 mg of powderwith a yield of 96.32%.

The resulting solid is Compound 1 Oxalate (Form A). The ratio ofCompound 1: oxalic acid in Compound 1 Oxalate (Form A) is 1:0.91 asdetermined by ion chromatography. The XPRD is shown in FIG. 116; the DSCand TGA are shown in FIG. 117; and the DVS is shown in FIG. 118.

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 Oxalate (Form A) and Compound 1 free baseare shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, Pattern A 98.2 1 w 1.2 millionlux- Pattern A 97.9 hrs Dark control Pattern A 98.3 Oxalate (Form 60°C., 1 w Form A 98.3 A) 40° C./75% RH, Form A 98.4 1 w 1.2 million luxForm A 98.2 hrs Dark control Form A 98.9

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 Oxalate (Form A) andCompound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 Oxalate (Form A) 3.76 1.95 1.84 4.860.75 3.73

Compound 1 Oxylate (Form B)

50 mg Compound 1 and 1.1 e.q. counter ion of oxalic acid in solid formwere weighed into 2 mL vials individually, and then 1 mL EtOAc solventwas added into the vial. The vial was placed on the thermo-mixer with astir bar and heated to 50° C. After keeping at 50° C. under constantstirring at 500 rpm for 21 hrs, the vial was then cooled to 25° C. Afterkeeping at 25° C. for 1 hr, the solids in suspension were isolated bycentrifugation and dried in the vacuum oven at 30° C. for 18 hrs.

The dried solids were characterized by PLM and XRPD (FIG. 119).

Example 24: Preparation of P-Aminosalicylate Salt of Compound 1

A P-Aminosalicylate Salt of Compound 1 may be prepared from Compound 1using the following exemplary method.

Compound 1 P-Aminosalicylate (Form A)

500 mg of Compound 1 was dissolved in 16.0 mL of acetone at 60° C. whilestirring at 500 rpm and held at 60° C. for 1.5 hrs. 1.1 eq.4-aminosalicylic acid in acetone (2.565 mL, 0.5 mol/L) was then addedinto the Compound 1 solution and incubated at 60° C. for 3 hrs, thencooled to 25° C. and held at 25° C. for overnight. This suspension wascentrifuged and the precipitate collected and washed with acetone. Theobtained wet product was vacuum dried at 25° C. for 72 hrs resulting in583.32 mg of powder with a yield of 83.37%.

The resulting solid is Compound 1 P-Aminosalicylate (Form A). The ratioof Compound 1: 4-aminosalicylic acid in Compound 1 P-Aminosalicylate(Form A) is 1:1.03 as determined by ion chromatography. The XPRD isshown in FIG. 120; the DSC and TGA are shown in FIG. 121; and the DVS isshown in FIG. 122.

Compound 1 P-Aminosalicylate (Form A) was analyzed by ¹H-NMR indeuterated DMSO resulting in the following chemical shifts: ¹H NMR (400MHz, DMSO-d₆) δ ppm 0.51-0.80 (m, 7H) 0.83-1.74 (m, 22H) 1.97-2.15 (m,3H) 2.34 (s, 1H) 2.68 (br t, J=8.69 Hz, 1H) 2.99-3.09 (m, 2H) 3.25 (s,4H) 4.83-5.10 (m, 2H) 5.88-6.11 (m, 3H) 6.76 (t, J=8.19 Hz, 1H) 6.90 (s,1H) 7.04 (s, 1H) 7.42 (d, J=8.63 Hz, 1H) 7.57 (s, 1H)

Chemical and Physical Stability Test

Chemical and physical stability testing was carried out using theprocedures set forth in Example 1. The chemical and physical stabilitytest results for Compound 1 P-Aminosalicylate (Form A) and Compound 1free base are shown in the following table:

Starting XRPD Final materials Conditions patterns purity Compound 1 60°C., 1 w Pattern A 98.2 40° C./75% RH, Pattern A 98.2 1 w 1.2 millionlux- Pattern A 97.9 hrs Dark control Pattern A 98.3 P- 60° C., 1 w FormA 91.5 aminosalicylate 40° C./75% RH, Form A 97.0 (Form A) 1 w 1.2million lux- Form A 95.7 hrs Dark control Form A 95.8

Solubility Tests in Simulated Gastric and Intestinal Fluids

Solubility Tests in Simulated Gastric and Intestinal Fluids was carriedout using the procedures set forth in Example 1. The solubility results(mg/mL) in bio-relevant solutions for Compound 1 P-Aminosalicylate (FormA) and Compound 1 free base are shown in the following table:

SGF FaSSIF FeSSIF (original (original (original pH = 1.82) pH = 6.51) pH= 4.99) Solute tested 24 h Final pH 24 h Final pH 24 h Final pH Compound1 4.44 3.10 0.05 6.48 0.84 5.11 P-Aminosalicylate 2.86 3.73 0.20 5.121.77 5.06 (Form A)

Compound 1 P-Aminosalicylate (Form B)

50 mg Compound 1 and 1.1 e.q. counter ion of 4-aminosalicylic acid insolid form were weighed into 2 mL vials individually, and then 1 mLsolvent EtOAc/ACN was added into the vial. The vial was placed on thethermo-mixer with a stir bar and heated to 50° C. After keeping at 50°C. under constant stirring at 500 rpm for 21 hrs, the vial was thencooled to 25° C. After keeping at 25° C. for 1 hr, the solids insuspension were isolated by centrifugation and dried in the vacuum ovenat 30° C. for 18 hrs.

The dried solids were characterized by PLM and XRPD (FIG. 123).

Example 25: Preparation of Maleate Salt of Compound 1

Maleate Salts of Compound 1 may be prepared from Compound 1 using thefollowing exemplary methods.

Compound 1 Maleate (Form A):

50 mg of compound 1 and 1.1 e.g. counter ion of maleic acid in solidform were weighed into 2 mL vials individually, and then 1 mL acetonesolvent was added into the vial. The vial was placed on the thermo-mixerwith a stir bar and heated to 50° C. After keeping at 50° C. underconstant stirring at 900 rpm for 18 hrs, the vial was then cooled to 25°C., After keeping at 25° C. for 1 hr, the solids in suspension wereisolated by centrifugation and dried in the vacuum oven at 30° C.overnight.

The obtained dried solids were characterized by PLM and XFPD (FIG. 124).

Example 26: Attempts to Prepare Salts of Compound 1

The following acids formed non-crystalline salts under some conditions:

Acid Solvent Maleic Acid Ethyl Acetate; IPA/Water (95:5 V:V) L-MalicAcid IPA/Water (95:5 V:V) Succinic Acid Acetone; ACN; IPA/Water (95:5V:V) Naphthalene-2-sulfonic IPA/Water (95:5 V:V) Acid Ascorbic AcidIPA/Water (95:5 V:V) Salicylic Acid Acetone; ACN; IPA/Water (95:5 V:V)Lactic Acid Acetone 2-Hydroxyethanesulfonic Acetone, Ethyl acetate acidD-Mandelic Acid Acetone; ACN; IPA/Water (95:5 V:V) Cyclamic AcidIPA/Water (95:5 V:V) Dichloroacetic acid Ethyl acetate; ACN; IPA/Water(95:5 V:V)

Although multiple conditions (shown below) were attempted, the acids inthe following table did not provide isolable salts of Compound 1.

Acid Solvent Hydrochloric Acid IPA/Water (95:5 V:V) Sulfuric AcidIPA/Water (95:5 V:V) Acetic Acid Acetone; Ethyl acetate; ACN; IPA/Water(95:5 V:V) Succinic Acid Ethyl Acetate Pamoic Acid Acetone; Ethylacetate; ACN; IPA/Water (95:5 V:V) Oleic Acid Acetone; Ethyl acetate;ACN; IPA/Water (95:5 V:V) L-Lysine Acid Acetone; Ethyl acetate; ACN;IPA/Water (95:5 V:V) L-Arginine Acetone; Ethyl acetate; ACN; IPA/Water(95:5 V:V) L-Aspartic Acid Acetone; Ethyl acetate; ACN; IPA/Water (95:5V:V) Mucic Acid Acetone; Ethyl acetate; ACN; IPA/Water (95:5 V:V)Hipuric Acid Acetone; Ethyl acetate; ACN; IPA/Water (95:5 V:V)L-Pyroglutamic Acetone; Ethyl acetate; ACN; IPA/Water (95:5 V:V) AcidGluconic Acid Acetone; Ethyl acetate; ACN; IPA/Water (95:5 V:V) Glyconic Acid Acetone; Ethyl acetate; ACN; IPA/Water (95:5 V:V) Lactic AcidEthyl acetate; ACN; IPA/Water (95:5 V:V) D-Mandelic Acid Ethyl AcetateLactobionic Acid Acetone; Ethyl Acetate; ACN; IPA/Water (95:5 V:V)Alginic Acid Acetone; Ethyl Acetate; ACN; IPA/Water (95:5 V:V)Glycerophosphoric Acetone; Ethyl Acetate; ACN; IPA/Water (95:5 V:V) AcidDL-Valine Acetone; Ethyl Acetate; ACN; IPA/Water (95:5 V:V) DL-LeucineAcetone; Ethyl Acetate; ACN; IPA/Water (95:5 V:V) L-Isoleucine Acetone;Ethyl Acetate; ACN; IPA/Water (95:5 V:V)

Experimental conditions: For each of the twenty acids listed in thetable above, four solvents (acetone, EtOAc, ACN and IPA/water (95/5,V/V)) were used according to following procedure to determine whetherisolable salts of Compound 1 were provided by the particularsolvent-acid combination.

Approximately 50 mg of Compound 1 and 1.1 molar equivalents of the acidwere placed in a 2 mL vial. Approximately 1 mL solvent was added intothe vial. The vials were placed on the thermomixer with a stir bar andheated to 50° C. After stirring (500 rpm) at 50° C. for 21 hrs, thevials were cooled to 25° C. and held at 25° C. for 1 hr and vials weremonitored for the formation of solids. None of the experiments providedsolids after stirring for approximately one hour. For each experiment,the solvent was evaporated in vacuum oven at 30° C. Under theseconditions, none of the acids listed in the table above provided anisolable salt of Compound 1.

Example 27. Bulk Density for salts of Compound 1. Bulk Tapped DensityDensity Salt Form (g/mL) (g/mL) Citrate A 0.49 0.70 Phosphate A 0.150.33 Tartrate A 0.13 0.32 HBr A 0.27 0.50 Free Base A 0.25 0.45

INCORPORATION BY REFERENCE

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What is claimed is:
 1. A citrate salt of Compound 1.